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Review Article

Molecular Neurobiology of Alzheimer's Disease (Syndrome?)

Pages 177-213 | Received 17 Jan 1997, Accepted 16 Jun 1997, Published online: 03 Jul 2009

References

  • Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr Scand 1987; 76: 465–79
  • Evans DA, Funkenstein HH, Albert MS, Scherr PA, Cook NR, Chown MJ, et al. Prevalence of Alzheimer's disease in a community population of older persons: higher than previously reported. JAMA 1989; 262: 2551–6
  • Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, et al. Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 1992; 42: 115–9
  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984; 34: 939–44
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders.4th ed. American Psychiatric Association, Washington, DC 1994
  • Khachaturian ZS. Diagnosis of Alzheimer's disease. Arch Neurol 1985; 42: 1097–105
  • Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brown-Lee LM, et al. The Consortium to Establish a Registry for Alzheimer's Disease, (CERAD), part II: Standardization of the neuropathologic assessment of Alzheimer's, disease. Neurology 1991; 41: 479–86
  • Alzheimer A. Über eine eigenartige Erkrankung der Hirnrinde. Allg Z Psychiatr 1907; 64: 146–8
  • Glenner GG, Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885–90
  • Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 1985; 82: 4245–9
  • Arriagada PV, Marzloff K, Hyman BT. Distribution of Alzheimer-type pathologic changes in nondemented elderly individuals matches the pattern in Alzheimer's disease. Neurology 1992; 42: 1681–8
  • Berg L, McKeel DW, Miller JP, Baty J, Morris JC. Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older. Arch Neurol 1993; 50: 349–58
  • Bierer LM, Hof PR, Purohit DP, Carlin L, Schmeidler J, Davis KL, et al. Neocortical neurofibrillary tangles correlate with dementia severity in Alzheimer's disease. Arch Neurol 1995; 52: 81–8
  • Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Harigaya Y. Diffuse type of senile plaques in the brains of Alzheimer-type dementia. Acta Neuropathol (Berl) 1988; 77: 113–9
  • Joachim CL, Morris JH, Selkoe DJ. Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. Am J Pathol 1989; 135: 309–19
  • Hyman BT, Marzloff K, Arriagada PV. The lack of accumulation of senile plaques or amyloid burden in Alzheimer's disease suggests a dynamic balance between amyloid deposition and resolution. J Neuropathol Exp Neurol 1993; 52: 594–600
  • Iqbal K, Grundke-Iqbal I. Ubiquitination and abnormal phosphorylation of paired helical filaments in Alzheimer's disease. Mol Neurobiol 1991; 5: 399–410
  • Iqbal K, Grundke-Iqbal I, Smith AJ, George L, Tung YC, Zaidi T. Identification and localization of a tau peptide to paired helical filaments of Alzheimer's disease. Proc Natl Acad Sci USA 1989; 86: 5646–50
  • Kidd M. Paired helical filaments in electron microscopy of Alzheimer's disease. Nature 1963; 197: 192–3
  • Wisniewski WM, Narang HK, Terry RD. Neurofibrillary tangles of paired helical filaments. J Neurol Sci 1976; 27: 173–81
  • Wisniewski HM, Merz PA, Iqbal K. Ultrastructure of paired helical filaments of Alzheimer's neurofibrillary tangle. J Neuropathol Exp Neurol 1984; 43: 643–56
  • Wischik CM, Crowther RA, Stewart M, Roth M. Subunit structure of paired helical filaments in Alzheimer's disease. J Cell Biol 1985; 100: 1905–12
  • Tomlinson BE, Blessed G, Roth M. Observations on the brains of non-demented old people. J Neurol Sci 1968; 7: 331–56
  • Zubenko GS, Moossy J, Martinez AJ, Rao GR, Kopp U, Hanin I. A brain regional analysis of morphologic and cholinergic abnormalities in Alzheimer's disease. Arch Neurol 1989; 46: 634–8
  • Giannakopoulos P, Hof PR, Mottier S, Michel JP, Bouras C. Neuropathological changes in the cerebral cortex of 1258 cases from a geriatric hospital: retrospective clinicopatholog-ical evaluation of a 10-year autopsy population. Acta Neuropathol (Berl) 1994; 87: 456–68
  • Hirano A, Malamud N, Elizan TS, Kurland LT. Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: further pathologic studies. Arch Neurol 1966; 15: 35–51
  • Wisniewski K, Jervis GA, Moretz RC, Wisniewski H. Alzheimer neurofibrillary tangles in diseases other than senile and presenile dementia. Ann Neurol 1979; 5: 288–94
  • Ishii T, Nakamura Y. Distribution and ultrastructure of Alzheimer's neurofibrillary tangles in postencephalitic parkinsonism of Economo type. Acta Neuropathol (Berl) 1981; 55: 59–62
  • Halper J, Scheithauer BW, Okazaki H, Laws ER, Jr. Meningioangiomatosis: a report of six cases with special reference to the occurrence of neurofibrillary tangles. J Neuropathol Exp Neurol 1986; 45: 426–46
  • McGeer PL, McGeer EG. Enzymes associated with the metabolism of, catecholamines, acetylcholine and GABA in human controls and patients with Parkinson's disease and Huntington's, chorea. J Neurochem 1976; 26: 65–76
  • Perry EK, Johnson M, Kerwin JM, Piggott MA, Court JA, Shaw PJ, et al. Convergent cholinergic activities in aging and Alzheimer's disease. Neurobiol Aging 1992; 13: 393–400
  • Mountjoy CQ, Tomlinson BE, Gibson RH. Amyloid and senile plaques and cerebral blood vessels, A semiquantitative investigation of a possible relationship. J Neurol Sci 1982; 57: 89–103
  • Vinters HV, Secor DL, Read SL, Frazee JG, Tomiyasu U, Stanley TM, et al. Microvasculature in brain biopsy specimens from patients with Alzheimer's disease: an immunohistochemical and ultrastructural study. Ultrastruct Pathol 1994; 18: 333–48
  • Tomlinson BE, Kitchener D. Granulovacuolar degeneration of hippocampal pyramidal cells. J Pathol 1972; 106: 165–85
  • Ball MJ. Neuronal, loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia: a quantitative, study. Acta Neuropathol, (Berl) 1977; 37: 111–8
  • Xu M, Shibayama H, Kobayashi H, Yamada K, Ishihara R, Zhao P, et al. Granulovacuolar degeneration in the hippocampal cortex of aging and demented patients—a quantitative study. Acta Neuropathol (Berl) 1992; 85: 1–9
  • Stieber A, Mourelatos Z, Gonatas NK. In Alzheimer's disease the Golgi apparatus of a population of neurons without neurofibrillary tangles is fragmented and atrophic. Am J Pathol 1996; 148: 415–26
  • Gibson PH, Tomlinson BE. Numbers of Hirano bodies in the hippocampus of normal and demented people with Alzheimer disease. J Neurol Sci 1977; 33: 199–206
  • Goldman JE. The association of actin with Hirano bodies. J Neuropathol Exp Neurol 1983; 42: 146–52
  • Zubenko GS, Moossy J, Kopp U. Neurochemical correlates of major depression in primary dementia. Arch Neurol 1990; 47: 209–14
  • Crystal HA, Horoupian DS, Katzman R, Jotkowitz S. Biopsy-proved Alzheimer disease presenting as a right parietal lobe syndrome. Ann Neurol 1982; 12: 186–8
  • Martin A, Brouwers P, Lalonde F, Cox C, Teleska P, Fedio P, et al. Towards a behavioral typology of Alzheimer's patients. J Clin Exp Neuropsychol 1986; 8: 594–610
  • Huff FJ, Becker JT, Belle SH, Nebes RD, Holland AL, Boller F. Cognitive deficits and clinical diagnosis of Alzheimer's disease. Neurology 1987; 37: 1119–24
  • Jagust WJ, Davies P, Tiller-Borcich JK, Reed BR. Focal Alzheimer's disease. Neurology 1990; 40: 14–9
  • Leverenz J, Sumi SM. Parkinson's disease in patients with Alzheimer's disease. Arch Neurol 1986; 43: 662–4
  • Ditter SM, Mirra SS. Neuropathologic and clinical features of Parkinson's disease in Alzheimer's disease patients. Neurology 1987; 37: 754–60
  • Förstl H, Burns A, Levy R, Cairns N, Luthert P, Lantos P. Neurologic signs in Alzheimer's disease: results of a prospective clinical and neuropathology study. Arch Neurol 1992; 49: 1038–42
  • Zubenko GS, Moossy J. Major depression in primary dementia: clinical and neuropathologic correlates. Arch Neurol 1988; 45: 1182–6
  • Zweig RM, Ross CA, Hedreen JC, Steele C, Cardillo JE, Whitehouse PJ, et al. The neuropathology of aminergic nuclei in Alzheimer's disease. Ann Neurol 1988; 24: 233–12
  • Chan-Palay V. Depression and senile dementia of the Alzheimer type: catecholamine changes in the locus coeruleus—basis for therapy. Dementia 1990; 1: 253–61
  • Alafuzoff I, Iqbal K, Friden H, Adolfsson R, Winblad B. Histopathological criteria for progressive dementia disorders: clinical-pathological correlation and classification by multivariate data analysis. Acta Neuropathol (Berl) 1987; 74: 209–25
  • Wade JPH, Mirsen TR, Hachinski VC, Fisman M, Lau C, Merskey H. The clinical diagnosis of Alzheimer's disease. Arch Neurol 1987; 44: 24–9
  • Joachim CL, Morris JH, Selkoe DJ. Clinically diagnosed Alzheimer's disease: autopsy results in 150 cases. Ann Neurol 1988; 24: 50–6
  • Morris JC, McKeel DW, Fulling K, Torack RM, Berg L. Validation of clinical diagnostic criteria for Alzheimer's disease. Ann Neurol 1988; 24: 17–22
  • Boller F, Lopez OL, Moossy J. Diagnosis of dementia: clinico-pathologic correlations. Neurology 1989; 39: 76–9
  • Mendez MF, Mastri AR, Sung JH, Frey WH, II. Clinically diagnosed Alzheimer disease: neuropathologic findings in 650 cases. Alzheimer Dis Assoc Disord 1992; 6: 35–43
  • Victoroff J, Mack WJ, Lyness SA, Chiu HC. Multicenter clinicopathological correlation in dementia. Am J Psychiatry 1995; 152: 1476–84
  • Boller F, Mizutani T, Roessmann U, Gambetti P. Parkinson, diseasedementia, and Alzheimer disease: clinicopathological correlations. Ann Neurol 1980; 7: 329–35
  • Hansen L, Salmon D, Galasko D, Masliah E, Katzman R, DeTeresa R, et al. The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity. Neurology 1990; 40: 1–8
  • Lippa CF, Smith TW, Swearer JM. Alzheimer's disease and Lewy body disease: a comparative clinicopathological study. Ann Neurol 1994; 35: 81–8
  • Perry EK, Marshall E, Perry RH, Irving D, Smith CJ, Blessed G, et al. Cholinergic and dopaminergic activities in senile dementia of Lewy body type. Alzheimer Dis Assoc Disord 1990; 4: 87–95
  • Perry EK, McKeith I, Thompson P, Marshall E, Kerwin J, Jabeen S, et al. Topography, extent, and clinical relevance of neurochemical deficits in dementia of Lewy body type, Parkinson's disease, and Alzheimer's disease. Ann NY Acad Sci 1991; 640: 197–202
  • Perry EK, Irving D, Kerwin JM, McKeith IG, Thompson P, Collerton D, et al. Cholinergic transmitter and neurotrophic activities in Lewy body dementia: similarity to Parkinson's and distinction from Alzheimer disease. Alzheimer Dis Assoc Disord 1993; 7: 69–79
  • Förstl H, Burns A, Luthert P, Cairns N, Levy R. The Lewy-body variant of Alzheimer's disease: clinical and pathological findings. Br J Psychiatry 1993; 162: 385–92
  • Langlais PJ, Thal L, Hansen L, Galasko D, Alford M, Masliah E. Neurotransmitters in basal ganglia and cortex of Alzheimer's disease with and without Lewy bodies. Neurology 1993; 43: 1927–34
  • McKeith I, Fairbairn A, Perry R, Thomson P, Perry E. Neuroleptic sensitivity in patients with senile dementia of Lewy body type. BMJ 1992; 305: 673–8
  • Weiner MF, Risser RC, Cullum CM, Honig L, White C, III, Speciale S, et al. Alzheimer's disease and its Lewy body variant: a clinical analysis of postmortem verified cases. Am J Psychiatry 1996; 153: 1269–73
  • Gravina SA, Ho L, Eckman CB, Long KE, Otvos L, Jr, Younkin LH, et al. Amyloid bˆ protein (Abˆ) in Alzheimer's disease brain: biochemical and immunocytochemical analysis with antibodies specific for forms ending at bˆ340 or bˆ342(43). J Biol Chem 1995; 270: 7013–6
  • Roher AE, Lowenson JD, Clarke S, Woods AS, Cotter RJ, Gowing E, et al. bˆ-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci USA 1993; 90: 10836–40
  • McGeer PL, Klegeris A, Walker DG, Yasuhara O, McGeer EG. Pathological proteins in senile plaques. Tohoku J Exp Med 1994; 174: 269–77
  • Saitoh T, Sunsdmo M, Roch JM, Kimura N, Cole G, Schubert D, et al. Secreted form of amyloid bˆ protein precursor is involved in the growth regulation of fibroblasts. Cell 1989; 58: 615–22
  • Koo EH, Park L, Selkoe DJ. Amyloid bˆ-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth. Proc Natl Acad Sci USA 1993; 90: 4748–52
  • Koh JY, Yang LL, Cotman CW. bˆ-Amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage. Brain Res 1990; 533: 315–20
  • Yankner BA, Caceres A, Duffy LK. Nerve growth factor potentiates the neurotoxicity of bˆ amyloid. Proc Natl Acad Sci USA 1990; 87: 9020–3
  • Price DL, Borchelt DR, Walker LC, Sisodia SS. Toxicity of synthetic Abˆ peptides and modeling of Alzheimer's disease. Neurobiol Aging 1992; 13: 623–5
  • Pike CJ, Burdick D, Walencewicz AJ, Glabe CG, Cotman CW. Neurodegeneration induced by bˆ-amyloid peptides in vitro: the role of peptide assembly state. J Neurosci 1993; 13: 1676–87
  • Hensley K, Carney JM, Mattson MP, Aksenova M, Harris M, Wu JF, et al. A model for bˆ-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 1994; 91: 3270–4
  • Lorenzo A, Yankner B. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by Congo red. Proc Natl Acad Sci USA 1994; 91: 12243–7
  • Walker LC, Kitt CA, Cork LC, Struble RG, Dellovade TL, Price DL. Multiple transmitter systems contribute neurites to individual senile plaques. J Neuropathol Exp Neurol 1988; 47: 138–44
  • Delacourte A, Defossez A. Alzheimer's disease: tau, proteins, the promoting factors of microtubule, assembly, are major components of paired helical, filaments. J Neurol, Sci 1986; 76: 173–86
  • Neve RL, Harris P, Kosik KS, Kurnit DM, Donlon TA. Identification of cDNA clones for the human microtubule-associated protein tau and chromosomal localization of the genes for tau and microtubule-associated protein 2. Brain Res 1986; 387: 271–80
  • Goedert M, Wischik CM, Crowther RA, Walker JE, Klug A. Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau. Proc Natl Acad Sci USA 1988; 85: 4051–5
  • Wolozin BL, Pruchnicki A, Dickson DW, Davies P. A neuronal antigen in the brains of Alzheimer's patients. Science 1986; 232: 648–50
  • Wolozin B, Davies P. Alzheimer-related neuronal protein A68: specificity and distribution. Ann Neurol 1987; 22: 521–6
  • Ksiezak-Reding H, Binder LI, Yen SH. Alzheimer disease proteins (A68) share epitopes with tau but show distinct biochemical properties. J Neurosci Res 1990; 25: 420–30
  • Lee VMY, Balin BJ, Otvos L, Jr, Trojanowski JQ. A68: a major subunit of paired helical filaments and derivatized forms of normal tau. Science 1991; 251: 675–8
  • Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J Biol Chem 1986; 261: 6084–9
  • Baudier J, Lee SH, Cole RD. Separation of the different microtubule-associated tau protein species from bovine brain and their mode II phosphorylation by Ca2+/phospholipid-dependent protein kinase C. J Biol Chem 1987; 262: 17584–90
  • Vandermeeren M, Mercken M, Vanmechelen E, Six J, Van de Voorde A, Martin JJ, et al. Detection of τ proteins in normal and Alzheimer's disease cerebrospinal fluid with a sensitive sandwich enzyme-linked immunosorbent assay. J Neurochem 1993; 61: 1828–34
  • Munroe WA, Southwick PC, Chang L, Scharre DW, Echols CL, Fu PC, et al. Tau protein in cerebrospinal fluid as an aid in the diagnosis of Alzheimer's disease. J Clin Lab Sci 1995; 25: 207–17
  • Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor [Letter]. Nature 1987; 325: 733–6
  • Yoshikai S, Sasaki H, Dohura K, Furuya H, Sakaki Y. Genomic organization of the human amyloid beta-protein precursor gene. Gene 1990; 87: 257–63
  • Ponte P, Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu D, Greenberg B, et al. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors [Letter]. Nature 1988; 331: 525–7
  • Tanzi RE, McClatchey Al, Lamperti ED, Villa-Komaroff L, Gusella JF, Neve RL. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease [Letter]. Nature 1988; 331: 528–30
  • König G, Mönning U, Czech C, Prior R, Banati R, Schreiter-Gasser U, et al. Identification and differential expression of a novel alternative splice isoform of the bˆA4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem 1992; 267: 10804–9
  • Selkoe DJ, Bell DS, Podlisny MB, Price DL, Cork LC. Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science 1987; 235: 873–7
  • Tanzi RE, St George-Hyslop PH, Haines JL, Polinsky RJ, Nee L, Foncin JF, et al. The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid beta-protein gene. Nature 1987; 329: 156–7
  • Selkoe DJ, Podlisny MB, Joachim CL, Vickers EA, Lee G, Fritz LC, et al. bˆ-Amyloid precursor protein of Alzheimer disease occurs as 110- to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci USA 1988; 85: 7341–5
  • Zimmermann K, Herget T, Salbaum JM. Localization of the putative precursor of Alzheimer's disease—specific amyloid at nuclear envelopes of adult human muscle. EMBO J 1988; 7: 367–72
  • Sprecher CA, Grant FJ, Grimm G, O'Hara PJ, Norris F, Norris K, et al. Molecular cloning of the cDNA for a human amyloid precursor protein homolog: evidence for a multigene family. Biochemistry 1993; 32: 4481–6
  • Wasco W, Gurubhagavatula S, Paradis M, Romano DM, Sisodia SS, Hyman BT, et al. Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid bˆ protein precursor. Nat Genet 1993; 5: 95–9
  • Smith RP, Higuchi DA, Broze GJ. Platelet coagulation factor, Xla-inhibitor, a form of Alzheimer amyloid precursor, protein. Science 1990; 248: 1126–8
  • Van Nostrand WE, Schmaier AH, Farrow JS, Cunningham DD. Protease nexin-II (amyloid bˆ-protein precursor): a platelet â-granule protein. Science 1990; 248: 745–8
  • Schubert D, Jin LW, Saitoh T, Cole G. The regulation of amyloid bˆ protein precursor secretion and its modulatory role in cell adhesion. Neuron 1989; 3: 689–94
  • Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE. Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the bˆ-amyloid precursor protein. Neuron 1993; 10: 243–54
  • Small DH, Nurcombe V, Reed G, Clarris H, Moir R, Beyreuther K, et al. A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci 1994; 14: 2117–27
  • Qiu WQ, Ferreira A, Miller C, Koo EH, Selkoe DJ. Cell-surface beta-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner. J Neurosci 1995; 15: 2157–67
  • Dyrks T, Weidermann A, Multhaup J, Salbaum JM, LeMaire HG, Kang J, et al. Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer's disease. EMBO J 1988; 7: 949–57
  • Oltersdorf T, Fritz LC, Schenk DB, Lieberburg I, Johnson-Wood KL, Beattie EC, et al. The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II. Nature 1989; 341: 144–7
  • Weidemann A, König G, Bunke D, Fischer P, Salbaum JM, Masters CL, et al. Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell 1989; 57: 115–26
  • Caporaso GL, Takei K, Gandy SE, Matteoli M, Mundigl O, Greengard P, et al. Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer bˆ/A4 amyloid precursor protein. J Neurosci 1994; 14: 3122–38
  • Hung AY, Selkoe DJ. Selective ectodomain phosphorylation and regulated cleavage of bˆ-amyloid precursor protein. EMBO J 1994; 13: 534–42
  • Haass C, Koo EH, Mellon A, Hung AY, Selkoe DJ. Targeting of cell-surface bˆ-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature 1992; 357: 500–3
  • Sisodia SS. bˆ-Amyloid precursor protein cleavage by a membrane-bound protease. Proc Natl Acad Sci USA 1992; 89: 6075–9
  • Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, et al. Cleavage of amyloid bˆ peptide during constitutive processing of its precursor. Science 1990; 248: 1122–4
  • Sisodia SS, Koo EH, Beyreuther K, Unterbeck A, Price DL. Evidence that bˆ-amyloid protein in Alzheimer's disease is not derived by normal processing. Science 1990; 248: 492–5
  • Anderson JP, Esch FS, Keim PS, Sambamurti K, Lieberburg I, Robakis NK. Exact cleavage site of Alzheimer amyloid precursor in neuronal PC-12 cells. Neurosci Lett 1991; 128: 126–8
  • Wang R, Meschia JF, Cotter RJ, Sisodia SS. Secretion of the bˆ/A4 amyloid precursor protein: identification of a cleavage site in cultured mammalian cells. J Biol Chem 1991; 266: 16960–4
  • Pasternack JM, Palmert MR, Usiak M, Wang R, Zurcher-Neely H, Gonzalez-DeWhitt PA, et al. Alzheimer's disease and control brain contain soluble derivatives of the amyloid protein precursor that end within the bˆ amyloid protein region. Biochemistry 1992; 31: 10936–40
  • Lai A, Sisodia SS, Trowbridge IS. Characterization of sorting signals in the bˆ-amyloid precursor protein cytoplasmic domain. J Biol Chem 1995; 270: 3565–73
  • Golde TE, Estus S, Younkin LH, Selkoe DJ, Younkin SG. Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science 1992; 255: 728–30
  • Yamazaki T, Koo EH, Selkoe DJ. Trafficking of cell-surface amyloid bˆ-protein, precursor II:, endocytosisrecycling, and lysosomal targeting detected by immunolocalization. J Cell Sci 1996; 109: 999–1008
  • Nukina N, Kanazawa I, Mannen T, Uchida Y. Accumulation of amyloid precursor protein and beta-protein immunoreactivities in axons injured by cerebral infarct. Gerontology 1992; 38: 10–4, suppl 1
  • Araujo DM, Cotman CW. Beta-amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer's disease. Brain Res 1992; 569: 141–5
  • Bendotti C, Forloni G, Morgan R, O'Hara BF, Oster-Granite L, Reeves RH, et al. Neuroanatomical localization and quantification of amyloid precursor protein mRNA by in situ hybridization in the brains of, normal, aneuploid and lesioned, mice. Proc Natl Acad Sci, USA 1988; 85: 3628–32
  • Rumble B, Retallack R, Hilbich C, Simms G, Multhaup G, Martins R, et al. Amyloid A4 protein and its precursor in Down's syndrome and Alzheimer's disease. N Engl J Med 1989; 320: 1446–52
  • Buxbaum JD, Oishi M, Chen HI, Pinkas-Kramarski R, Jaffee EA, Gandy SE, et al. Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor. Proc Natl Acad Sci USA 1992; 89: 10075–8
  • Nitsch RM, Blusztajn JK, Pittas AG, Slack BE, Growdon JH, Wurtman RJ. Evidence for a membrane defect in Alzheimer disease brain. Proc Natl Acad Sci USA 1992; 89: 1671–5
  • Querfurth HW, Selkoe DJ. Calcium ionophore increases amyloid beta peptide production by cultured cells. Biochemistry 1994; 33: 4450–61
  • Haltia M, Viitanen M, Sulkava R, Ala-Hurula V, Poyhonen M, Goldfarb L, et al. Chromosome 14—encoded Alzheimer's disease: genetic and clinicopathological description. Ann Neurol 1994; 36: 362–7
  • Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N, et al. Secreted amyloid bˆ-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 1996; 2: 864–70
  • Selkoe DJ. Amyloid p-protein and the genetics of Alzheimer's disease. J Biol Chem 1996; 271: 18295–8
  • Jarrett JT, Berger EP, Lansbury PT. The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 1993; 32: 4693–7
  • Iwatsubo T, Odaka S, Suzuki N, Mizusawa H, Nukina N, Ihara Y. Visualization of Abˆ42(43) and Abˆ40 in senile plaques with end-specific Abˆ-monoclonals: evidence that an initially deposited species is Abˆ42(43). Neuron 1994; 13: 45–53
  • Motter R, Vigo-Pelfrey C, Kholodenko D, Barbour R, Johnson-Wood K, Galasko D, et al. Reduction of bˆ-amyloid peptide42 in the cerebrospinal fluid of patients with Alzheimer's disease. Ann Neurol 1995; 38: 643–8
  • Buée L, Ding W, Anderson JP, Narindrasorasak S, Kisilevsky R, Boyle NJ, et al. Binding of vascular heparan sulfate proteoglycan to Alzheimer's amyloid precursor protein is mediated in part by the N-terminal region of A4 peptide. Brain Res 1993; 627: 199–204
  • Ghiso J, Matsubara E, Koudinov A, Choi-Miura NH, Tomita M, Wisniewski T, et al. The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to, SP-40, 40 (apolipoprotein, J), an inhibitor of the complement membrane-attack, complex. Biochem, J 1993; 293: 27–30
  • Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, et al. Apolipoprotein E: high-avidity binding to bˆ-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 1993; 90: 1977–81
  • Castanˆo EM, Prelli F, Wisniewski T, Golabek A, Kumar RA, Soto C, et al. Fibrillogenesis in Alzheimer's disease of amyloid bˆ peptides and apolipoprotein E. Biochem J 1995; 306: 599–604
  • Evans KC, Berger EP, Cho CG, Weisgraber KH, Lansbury PT. Apolipoprotein E is a kinetic but not a thermodynamic inhibitor of amyloid formation: implications for the pathogenesis and treatment of Alzheimer disease. Proc Natl Acad Sci USA 1995; 92: 763–7
  • Aisen PS, Davis KL. Inflammatory mechanisms in Alzheimer's disease: implications for therapy. Am J Psychiatry 1994; 151: 1105–13
  • McGeer PL, Rogers J, McGeer EG. Neuroimmune mechanisms in Alzheimer disease pathogenesis. Alzheimer Dis Assoc Disord 1994; 8: 149–58
  • Whitehouse PJ, Price DL, Struble RG, Clark AW, Coyle JT, DeLong MR. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 1982; 215: 1237–9
  • Arendt T, Bigl V, Arendt A, Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer's, disease, paralysis, agitans, and Korsakoff s, disease. Acta Neuropathol, (Berl) 1983; 61: 101–8
  • Saper CB, German DC, White CL. Neuronal pathology in the nucleus basalis and associated cell groups in senile dementia of the Alzheimer's type: possible role in cell loss. Neurology 1985; 35: 1089–95
  • Pope A, Hess HH, Lewin E. Microchemical pathology of the cerebral cortex in pre-senile dementias. Trans Am Neurol Assoc 1964; 89: 15–6
  • Davies P, Maloney AJF. Selective loss of central cholinergic neurons in Alzheimer's disease [Letter]. Lancet 1976; 2: 1403
  • Rossor MN, Garrett NJ, Johnson AL, Mountjoy CQ, Roth M, Iversen LL. A post-mortem study of the cholinergic and GABA systems in senile dementia. Brain 1982; 105: 313–30
  • Bird TD, Stranahan S, Sumi SM, Raskind M. Alzheimer's disease: choline acetyltransferase activity in brain tissue from clinical and pathological subgroups. Ann Neurol 1983; 14: 284–93
  • Bowen DM, Allen SJ, Benton JS, Goodhardt MF, Haan EA, Sims NR, et al. Biochemical assessment of serotonergic and cholinergic dysfunction and cerebral atrophy in Alzheimer's disease. J Neurochem 1983; 41: 266–72
  • Sims NR, Bowen DM, Allen SJ, Smith CCT, Neary D, Thomas DJ, et al. Presynaptic cholinergic dysfunction in patients with dementia. J Neurochem 1983; 40: 503–9
  • Perry EK, Tomlinson BE, Blessed G, Bergmann K, Gibson PH, Perry RH. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J 1978; 2: 1457–9
  • Mountjoy CQ, Rossor MN, Iversen LL, Roth M. Correlation of cortical cholinergic and GABA deficits with quantitative neuropathological findings in senile dementia. Brain 1984; 107: 507–18
  • Neary D, Snowden JS, Mann DMA, Bowen DM, Sims NR, Northen B, et al. Alzheimer's disease: a correlative study. J Neurol Neurosurg Psychiatry 1986; 49: 229–37
  • Dickson DW, Crystal HA, Bevona C, Honer W, Vincent I, Davies P. Correlations of synaptic and pathological markers with cognition of the elderly. Neurobiol Aging 1995; 16: 285–304
  • Drachman DA, Leavitt J. Human memory and the cholinergic system. Arch Neurol 1974; 30: 113–21
  • Bartus RT, Dean RL, Beer B, Lippa AS. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217: 408–17
  • Blusztajn JK, Wurtman RJ. Choline and cholinergic neurons. Science 1983; 221: 614–20
  • Wurtman RJ, Blusztajn JK, Maire JC. 'Autocannibalism' of choline-containing membrane phospholipids in the pathogenesis of Alzheimer's disease: an hypothesis. Neurochem Int 1985; 7: 369–72
  • Tucek S. Problems in the organization and control of acetylcholine synthesis in brain neurons. Prog Biophys Mol Biol 1984; 44: 1–46
  • Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci 1992; 15: 117–22
  • Zeisel SH. Choline: an important nutrient in brain, development, liver function and, carcinogenesis. J Am Coll, Nutr 1992; 11: 473–81
  • Cohen BM, Renshaw PF, Stoll AL, Wurtman RJ, Yurgelun-Todd D, Babb SM. Decreased brain choline uptake in older adults. JAMA 1995; 274: 902–7
  • Brinkman S, Sniff R, Meyer J, Vroulis G, Shaw T, Gordon JR, et al. Lecithin and memory training in suspected Alzheimer's disease. J Gerontol 1982; 37: 4–9
  • Kaye W, Sitaram N, Weingartner H, Ebert M, Smallberg S, Gillin J. Modest facilitation of memory in dementia with combined lecithin and anticholinesterase treatment. Biol Psychiatry 1982; 17: 275–80
  • Pomara N, Domino E, Yoon H, Brickman S, Tamminga C, Gershon S. Failure of single dose lecithin to alter aspects of central cholinergic activity in Alzheimer's disease. J Clin Psychiatry 1983; 44: 293–5
  • Wettstein A. No effect from double-blind trial of physostigmine and lecithin in Alzheimer's disease. Ann Neurol 1983; 13: 210–2
  • Smith R, Vroulis G, Johnson R, Morgan R. Comparison of therapeutic response to long-term treatment with lecithin vs piracetam plus lecithin in patients with Alzheimer's disease. Psychopharmacol Bull 1984; 20: 542–5
  • Little A, Levy R, Chuaqui-Kidd P, Hand D. A, double-blind, placebo-controlled trial of high-dose lecithin in Alzheimer's, disease. J Neurol Neurosurg, Psychiatry 1985; 48: 736–42
  • Raiteri M, Leardi R, Marchi M. Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain. J Pharmacol Exp Ther 1984; 228: 209–14
  • Mash DC, Flynn DD, Potter LT. Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. Science 1985; 228: 1115–7
  • Bonner TI. The molecular basis of muscarinic receptor diversity. Trends Pharmacol Sci 1989; 10: 148–51
  • McKinney M, Anderson DJ, Vella-Rountree L, Connolly T, Miller JH. Pharmacological profiles for rat cortical M1 and M2 muscarinic receptors using selective antagonists: comparison with N1E-115 muscarinic receptors. J Pharmacol Exp Ther 1991; 257: 1121–9
  • Greenamyre JT, Maragos WF. Neurotransmitter receptors in Alzheimer disease. Cerebrovasc Brain Metab Rev 1993; 5: 61–94
  • Smith CJ, Perry EK, Perry RH, Fairbairn AF, Birdsall NJM. Guanine nucleotide modulation of muscarinic receptor binding in postmortem human brain—a preliminary study in Alzheimer's disease. Neurosci Lett 1987; 82: 227–32
  • Flynn DD, Weinstein DA, Mash DC. Loss of high-affinity agonist binding to M1 muscarinic receptors in Alzheimer's disease: implications for the failure of cholinergic replacement therapies. Ann Neurol 1991; 29: 256–62
  • Marin DB, Davis KL. Experimental therapeutics. Psychopharmacology: the fourth generation of progress, FE Bloom, DJ Kupfer. Raven, New York 1995; 1417–26
  • Woolf NJ, Butcher LL. Cholinergic systems: synopsis of anatomy and overview of physiology and pathology. The biological substrates of Alzheimer's disease, AB Scheibel, AF Wechsler. Academic, New York 1989; 73–86
  • Flynn DD, Mash DC. Characterization of l-[3H]nicotine binding in human cerebral cortex: comparison between Alzheimer's disease and normal. J Neurochem 1986; 47: 1948–54
  • Shimohama S, Taniguchi T, Fujiwara M, Kameyama M. Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer-type dementia. J Neurochem 1986; 46: 288–93
  • Whitehouse PJ, Martino AM, Antuono PG, Lowenstein PR, Coyle JT, Price DL, et al. Nicotinic acetylcholine binding sites in Alzheimer's disease. Brain Res 1986; 371: 146–51
  • Perry EK, Perry RH, Smith CJ, Dick DJ, Candy JM, Edwardson JA, et al. Nicotinic receptor abnormalities in Alzheimer's and Parkinson's diseases. J Neurol Neurosurg Psychiatry 1987; 50: 806–9
  • Araujo DM, Lapchak PA, Robitaille Y, Gauthier S, Quirion R. Differential alteration of various cholinergic markers in cortical and subcortical regions of human brain in Alzheimer's disease. J Neurochem 1988; 50: 1914–23
  • Rinne JO, Myllykylä P, Lönnberg P, Marjamäki P. A postmortem study of brain nicotinic receptors in Parkinson's and Alzheimer's disease. Brain Res 1991; 547: 167–70
  • Zubenko GS, Moossy J, Martinez AJ, Rao GR, Claassen D, Rosen J, et al. Neuropathological and neurochemical correlates of psychosis in primary dementia. Arch Neurol 1991; 48: 619–24
  • Zubenko GS. Clinicopathological and neurochemical correlates of major depression and psychosis in primary dementia. Int Psychogeriatr 1996; 8: 219–23
  • Tomlinson BE, Irving D, Blessed G. Cell loss in the locus coeruleus in senile dementia of Alzheimer type. J Neurol Sci 1981; 49: 419–28
  • Iversen LL, Rossor MN, Reynolds GP, Hills R, Roth M, Mountjoy CQ, et al. Loss of pigmented dopamine-bˆ-hydroxylase positive cells from locus coeruleus in senile dementia of Alzheimer's type. Neurosci Lett 1983; 39: 95–100
  • Curcio CA, Kemper T. Nucleus raphe dorsalis in dementia of the Alzheimer type: neurofibrillary changes and neuronal packing density. J Neuropathol Exp Neurol 1984; 43: 359–68
  • Yamamoto T, Hirano A. Nucleus raphe dorsalis in Alzheimer's disease: neurofibrillary tangles and loss of large neurons. Ann Neurol 1985; 17: 573–7
  • Cross AJ, Crow TJ, Perry EK, Perry RH, Blessed G, Tomlinson BE. Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease. Br Med J (Clin Res Ed) 1981; 282: 93–4
  • Winblad B, Adolfsson R, Carlsson A, Gottfries CG. Biogenic amines in brains of patients with Alzheimer's disease. Alzheimer's disease: a report of progress in research (aging), S Corkin, KL Davis, JH Growdon, E Usdin, RJ Wurtman. Raven, New York 1982; 25–33
  • Rossor M, Iversen LL. Non-cholinergic neurotransmitter abnormalities in Alzheimer's disease. Br Med Bull 1986; 42: 70–4
  • Bowen DM, Benton JS, Spillane JA, Smith CC, Allen SJ. Choline acetyltransferase activity and histopathology of frontal neocortex from biopsies of demented patients. J Neurol Sci 1982; 57: 191–202
  • Palmer AM, Francis PT, Bowen DM, Benton JS, Neary D, Mann DMA, et al. Catecholaminergic neurons assessed ante-mortem in Alzheimer's disease. Brain Res 1987; 414: 365–75
  • Peroutka SJ. 5-Hydroxytryptamine receptor subtypes:, molecular, biochemical and physiological, characterization. Trends, Neurosci 1988; 11: 496–500
  • Hyman SE, Nestler EJ. The molecular foundations of psychiatry. American Psychiatric Press, Washington, DC 1993
  • Davies MF, Deisz RA, Prince DA, Peroutka SJ. Two distinct effects of 5-hydroxytryptamine on single cortical neurons. Brain Res 1987; 423: 347–52
  • Leysen JE, Van Gompel P, Verwimp M, Niemeyeers CJ. Role and localization of serotonin-2 receptor binding sites: effects of neuronal lesions. CNS receptors: from molecular pharmacology to behavior, P Mandel, FV DeFeudis. Raven, New York 1983; 373–83
  • Cross AJ, Crow TJ, Ferrier IN, Johnson JA, Bloom SR, Corsellis JAN. Serotonin receptor changes in dementia of the Alzheimer type. J Neurochem 1984; 43: 1574–81
  • Cross AJ, Crow TJ, Ferrier IN, Johnson JA. The selectivity of the reduction of serotonin S2 receptors in Alzheimer-type dementia. Neurobiol Aging 1986; 7: 3–7
  • Middlemiss DN, Palmer AN, Edel N, Bowen DM. Binding of the novel serotonin agonist 8-hydroxy-2-(di-n-propylamino) tetralin in normal and Alzheimer brain. J Neurochem 1986; 46: 993–6
  • Jansen KLR, Faull RLM, Dragunow M, Synek BL. Alzheimer's disease: changes in hippocampal N-methyl-d-aspartate, quisqualate, neurotensin, adenosine, benzodiazepine, serotonin and opioid receptors—an autoradiographic study. Neuro-science 1990; 39: 613–27
  • Cross AJ, Crow TJ, Johnson JA, Perry EK, Perry RH, Blessed G, et al. Studies on neurotransmitter receptor systems in the neocortex and hippocampus in senile dementia of the Alzheimer-type. J Neurol Sci 1984; 64: 109–17
  • Reynolds GP, Arnold L, Rossor MN, Iversen LL, Mountjoy CQ, Roth M. Reduced binding of [3H]ketanserin to cortical 5-HT2 receptors in senile dementia of the Alzheimer type. Neurosci Lett 1984; 44: 47–51
  • Quirion R, Martel JC, Robitaille Y, Etienne P, Wood P, Nair NPV, et al. Neurotransmitter and receptor deficits in senile dementia of the Alzheimer type. Can J Neurol Sci 1986; 13: 503–10, 4 suppl
  • Cheng AVT, Ferrier IN, Morris CM, Jabeen S, Sahgal A, McKeith IG, et al. Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases. J Neurol Sci 1991; 106: 50–5
  • Gottfries CG, Karlsson I, Nyth AL. Treatment of depression in elderly patients with and without dementia disorders. Int Clin Psychopharmacol 1992; 5: 55–64
  • Bowen DM, Francis PT, Pangalos MN, Stephens PH, Procter AW. Treatment strategies for Alzheimer's disease. Lancet 1992; 339: 132–3
  • Kalaria RN, Andorn AC, Tabaton M, Whitehouse PJ, Harik SI, Unnerstall JR. Adrenergic receptors in aging and Alzheimer's disease: increased (bˆ2-receptors in prefrontal cortex and hippocampus. J Neurochem 1989; 53: 1772–81
  • O'Neill C, Fowler CJ, Wiehager B, Cowburn RF, Alafuzoff I, Winblad B. Coupling of human brain cerebral cortical â2-adrenoceptors to GTP-binding proteins in Alzheimer's disease. Brain Res 1991; 563: 39–43
  • Meana JJ, Barturen F, Garro MA, García-Sevilla JA, Fontán A, Zarranz JJ. Decreased density of presynaptic â2-adrenoceptors in postmortem brains of patients with Alzheimer's disease. J Neurochem 1992; 58: 1896–904
  • Lewis DA, Morrison JH. Noradrenergic innervation of monkey prefrontal cortex: a dopamine-bˆ-hydroxylase immunohistochemical study. J Comp Neurol 1989; 282: 317–30
  • Civelli O, Bunzow JR, Grandy DK, Zhou QY, Van Tol HHM. Molecular biology of the dopamine receptors. Eur J Pharmacol Mol Pharmacol Sect 1991; 207: 277–86
  • Starke K, Göthert M, Kilbinger H. Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 1989; 69: 864–989
  • Mann DMA, Yates PO, Marcyniuk B. Dopaminergic neurotransmitter systems in Alzheimer's disease and in Down's syndrome in middle age. J Neurol Neurosurg Psychiatry 1987; 50: 341–4
  • Torak RM, Morris JC. The association of ventral tegmental area histopathology with adult dementia. Arch Neurol 1988; 45: 497–501
  • Adolfsson R, Gottfries CG, Roos BE, Winblad B. Changes in the brain catecholamine in patients with dementia of Alzheimer type. Br J Psychiatry 1979; 135: 216–23
  • Yates CM, Allison Y, Simpson J, Maloney AFJ, Gordon A. Dopamine in Alzheimer's disease and senile dementia. Lancet 1979; 2: 851–2
  • Arai H, Kosaka K, Iizuka R. Changes of biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia. J Neurochem 1984; 43: 388–93
  • Cross AJ, Crow TJ, Ferrier IN, Johnson JA, Markakis D. Striatal dopamine receptors in Alzheimer-type dementia. Neurosci Lett 1984; 52: 1–6
  • Cortés R, Probst A, Palacios JM. Decreased densities of dopamine D1 receptors in the putamen and hippocampus in senile dementia of the Alzheimer type. Brain Res 1988; 475: 164–7
  • De Keyser J, Ebinger G, Vauquelin G. D1-dopamine receptor abnormality in frontal cortex points to a functional alteration of cortical cell membranes in Alzheimer's disease. Arch Neurol 1990; 47: 761–3
  • Rinne JO, Säkö Ë, Paljärvi L, Mölsä PK, Rinne UK. Brain dopamine D-1 receptors in senile dementia. J Neurol Sci 1986; 73: 219–30
  • Emson PC, Lindvall O. Neuroanatomical aspects of neurotransmitters affected in Alzheimer's disease. Br Med Bull 1986; 42: 57–62
  • Francis PT, Webster MT, Chessel IP, Holmes C, Stratmann GC, Procter AW, et al. Neurotransmitters and second messengers in aging and Alzheimer's disease. Ann NY Acad Sci 1993; 695: 19–26
  • White WF, Nadler JV, Hamberger A, Cotman CW, Cummins JT. Glutamate as a transmitter of hippocampal perforant path. Nature 1977; 270: 356–7
  • Stone TW. Amino acids as neurotransmitters of corticofugal neurones in the rat: a comparison of glutamate and aspartate. Br J Pharmacol 1979; 67: 545–51
  • Storm-Mathisen J, Iversen LL. Uptake of [3H]glutamic acid in excitatory nerve endings: light and electron microscopic observations in the hippocampal formation of the rat. Neuroscience 1979; 4: 1237–53
  • Zaczek R, Hedreen JC, Coyle JT. Evidence for a hippocampalseptal glutamatergic pathway in the rat. Exp Neurol 1979; 65: 145–56
  • Streit P. Glutamate and aspartate as transmitter candidates for systems of the cerebral cortex. Cerebralcortex, EJ Jones, A Peters. Plenum, New York 1984; vol. 2.: 119–43
  • Procter AW, Palmer AM, Stratmann GC, Bowen DM. Glutamate/aspartate-releasing neurons in Alzheimer's disease [Letter]. N Engl J Med 1986; 314: 1711–2
  • Ellison DW, Beal MF, Mazurek MF, Bird ED, Martin JB. A postmortem study of amino acid neurotransmitters in Alzheimer's disease. Ann Neurol 1986; 20: 616–21
  • Sasaki H, Muramoto O, Kanazawa I, Arai H, Kosaka K, Iizuka R. Regional distribution of amino acid transmitters in postmortem brains of presenile and senile dementia of Alzheimer type. Ann Neurol 1986; 19: 263–9
  • Greenamyre JT, Young AB. Excitatory amino acids and Alzheimer's disease. Neurobiol Aging 1989; 10: 593–602
  • Watkins JC, Evans RH. Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol 1981; 21: 165–204
  • Monaghan DT, Holets VR, Toy DW, Cotman CW. Anatomical distributions of four pharmacologically distinct 3H-l-glutamate binding sites. Nature 1983; 306: 176–9
  • Greenamyre JT, Penney JB, Young AB, D'Amato CL, Hicks SP, Shoulson I. Alterations of l-glutamate binding in Alzheimer's and Huntington's diseases. Science 1985; 227: 1496–9
  • Jansen KLR, Dragunow M, Faull RLM. [3H]Glycine binding sites, NMDA and PCP receptors have similar distributions in the human hippocampus: an autoradiographic study. Brain Res 1989; 482: 174–8
  • Harris EW, Ganong AH, Cotman CW. Long-term potentiation in the hippocampus involves activation of N-methyl-d-aspartate receptors. Brain Res 1984; 323: 132–7
  • Collingridge GL. Long term potentiation in the hippocampus: mechanisms of initiation and modulation by neurotransmitters. Trends Pharmacol Sci 1985; 6: 407–11
  • Morris RGM, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, AP5. Nature 1986; 319: 774–6
  • Meldrum B, Garthwaite J. Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 1990; 11: 379–87
  • Faden AI, Demediuk P, Panter SS, Vink R. The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 1989; 244: 798–800
  • Benveniste H. The excitotoxin hypothesis in relation to cerebral ischemia. Cerebrovasc Brain Metab Rev 1991; 3: 213–45
  • Maragos WF, Greenamyre JT, Penney JB, Young AB. Glutamate dysfunction in Alzheimer's disease: an hypothesis. Trends Neurosci 1987; 10: 65–8
  • Greenamyre JT, Maragos WF, Albin RL, Penney JB, Young AB. Glutamate transmission and toxicity in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 1988; 12: 421–30
  • Dodd PR, Scott HL, Westphalen RI. Excitotoxic mechanisms in the pathogenesis of dementia. Neurochem Int 1994; 25: 203–19
  • Maragos WF, Chu DCM, Young AB, D'Amato CJ, Penney JB. Loss of hippocampal [3H]TCP binding in Alzheimer's disease. Neurosci Lett 1987; 74: 371–6
  • Monaghan DT, Geddes JW, Yao D, Chung C, Cotman CW. [3H]TCP binding sites in Alzheimer's disease. Neurosci Lett 1987; 73: 197–200
  • Chalmers DT, Dewar D, Graham DI, Brooks DN, McCulloch J. Differential alterations of cortical glutamatergic binding sites in senile dementia of the Alzheimer type. Proc Natl Acad Sci USA 1990; 87: 1352–6
  • Ninomiya H, Fukunaga R, Taniguchi T, Fujiwara M, Shimohama S, Kameyama M. [3H]N-[1-(2-Thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in human frontal cortex: decreases in Alzheimer-type dementia. J Neurochem 1990; 54: 526–32
  • Penney JB, Maragos WF, Greenamyre JT, Debowey DL, Hollingsworth Z, Young AB. Excitatory amino acid binding sites in the hippocampal region of Alzheimer's disease and other dementias. J Neurol Neurosurg Psychiatry 1990; 53: 314–20
  • Ulas J, Brunner LC, Geddes JW, Choe W, Cotman CW. N-Methyl-d-aspartate receptor complex in the hippocampus of elderly, normal individuals and those with Alzheimer's disease. Neuroscience 1992; 49: 45–61
  • Dewar D, Chalmers DT, Shand A, Graham DI, McCulloch J. Selective reduction of quisqualate (AMPA) receptors in Alzheimer's cerebellum. Ann Neurol 1990; 28: 805–10
  • Dewar D, Chalmers DT, Graham DI, McCulloch J. Glutamate metabotropic and AMPA binding sites are reduced in Alzheimer's disease: an autoradiographic study of the hippocampus. Brain Res 1991; 553: 58–64
  • Backus KH, Kettenmann H, Schachner M. Pharmacological characterization of the glutamate receptor in cultured astrocytes. J Neurosci Res 1989; 22: 274–82
  • Usowicz MM, Gallo V, Cull-Candy SG. Multiple conductance channels in type-2 cerebellar astrocytes activated by excitatory amino acids. Nature 1989; 339: 380–3
  • Glaum SR, Holzwarth JA, Miller RJ. Glutamate receptors activate Ca2+ mobilization and Ca2+ influx into astrocytes. Proc Natl Acad Sci USA 1990; 87: 3454–8
  • Tanabe Y, Masu M, Ishii T, Shigemoto R, Nakanishi S. A family of metabotropic glutamate receptors. Neuron 1992; 8: 169–79
  • MacVicar BA, Baker K, Crichton SA. Kainic acid evokes a potassium efflux from astrocytes. Neuroscience 1988; 25: 721–5
  • Nicoletti F, Meek JL, Iadarola MJ, Chuang DM, Roth BL, Costa E. Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem 1986; 46: 40–6
  • Schoepp DD, Johnson BG, Monn JA. Inhibition of cyclic AMP formation by a selective metabotropic glutamate receptor agonist. J Neurochem 1992; 58: 1184–6
  • Geddes JW, Monaghan DT, Cotman CW, Lott IT, Kim RC, Chui HC. Plasticity of hippocampal circuitry in Alzheimer disease. Science 1985; 230: 1179–81
  • Roberts E, Chase TN, Tower DB. GABA in nervous system function. Raven, New York 1976
  • Walker LC, Kitt CA, Struble RG, Schmechel DE, Oertel WH, Cork LC, et al. Glutamic acid decarboxylase-like immunore-active neurites in senile plaques. Neurosci Lett 1985; 59: 165–9
  • Hardy J, Cowburn R, Barton A, Reynolds G, Dodd P, Wester P, et al. A disorder of cortical GABAergic innervation in Alzheimer's disease. Neurosci Lett 1987; 73: 192–6
  • Simpson MDC, Cross AJ, Slater P, Deakin JFW. Loss of cortical GABA uptake sites in Alzheimer's disease. J Neural Transm 1988; 71: 219–26
  • Davies P, Katzman R, Terry RD. Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer disease and Alzheimer senile dementia. Nature 1980; 288: 279–80
  • Rossor MN, Emson PC, Mountjoy CQ, Roth M, Iversen LL. Reduced amounts of immunoreactive somatostatin in the temporal cortex in senile dementia of Alzheimer type. Neurosci Lett 1980; 20: 373–7
  • Beal MF, Mazurek MF, Tran VT, Chattha G, Bird ED, Martin JB. Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease. Science 1985; 229: 289–91
  • Candy JM, Gasciogne AD, Biggins JA, Smith AI, Perry RH, Perry EK, et al. Somatostatin immunoreactivity in cortical and some subcortical regions in Alzheimer's disease. J Neurol Sci 1985; 71: 315–23
  • Roberts GW, Crow TJ, Polak JM. Location of neuronal tangles in somatostatin neurones in Alzheimer's disease. Nature 1985; 314: 92–4
  • Taminga CA, Foster NL, Chase TN. Reduced brain somatostatin levels in Alzheimer's disease. N Engl J Med 1985; 313: 1294–5
  • Schmechel DE, Vickrey BG, Fitzpatrick D, Elde RP. GABAergic neurons of mammalian cerebral cortex: widespread subclass denned by somatostatin content. Neurosci Lett 1984; 47: 227–32
  • Sivilotti L, Nistri A. GABA receptor mechanisms in the central nervous system. Prog Neurobiol 1991; 36: 35–92
  • Vogt BA, Crino PB, Volicer L. Laminar alterations in γ-aminobutyric, acid, muscarinic and bˆ adrenoreceptors and neuron degeneration in cingulate cortex in Alzheimer's, disease. J Neurochem 1991; 57: 282–90
  • Chu DC, Penney JB, Young AB. Cortical GABAB and GABAA receptors in Alzheimer's disease: a quantitative autoradiographic study. Neurology 1987; 37: 1454–9
  • Phelps ME, Huang SC, Hoffman EJ, Selin C, Sokoloff L, Kuhl DE. Tomographic measurement of local cerebral glucose metabolic rate in humans with (F-18)2-fluoro-2-deoxy-d-glucose: validation of method. Ann Neurol 1979; 6: 371–88
  • Reivich M, Kuhl D, Wolf A, Greenberg J, Phelps M, Ido T, et al. The 18F-fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res 1979; 44: 127–37
  • McGeer EG, Peppard RP, McGeer PL, Tuokko H, Crockett D, Parks R, et al. 18Fluorodeoxyglucose positron emission tomography studies in presumed Alzheimer cases, including 13 serial scans. Can J Neurol Sci 1990; 17: 1–11
  • Kumar A, Schapiro MB, Grady CL, Haxby JV, Wagner E, Salerno JA, et al. High-resolution PET studies in Alzheimer's disease. Neuropsychopharmacology 1991; 4: 35–46
  • Smith GS, De Leon MJ, George AE, Kluger A, Volkow ND, McRae T, et al. Topography of cross-sectional and longitudinal glucose metabolic deficits in Alzheimer's disease: pathophysiologic implications. Arch Neurol 1992; 49: 1142–50
  • Murphy DGM, Bottomley PA, Salerno JA, DeCarli C, Mentis MJ, Grady CL, et al. An in vivo study of phosphorus and glucose metabolism in Alzheimer's disease using magnetic resonance spectroscopy and PET. Arch Gen Psychiatry 1993; 50: 341–9
  • Mielke R, Herholz K, Grond M, Kessler J, Heiss WD. Clinical deterioration in probable Alzheimer's disease correlates with progressive metabolic impairment of association areas. Dementia 1994; 5: 36–41
  • Minoshima S, Frey KA, Koeppe RA, Foster NL, Kuhl DE. A diagnostic approach in Alzheimer's disease using three-dimensional stereotactic surface projections of fluorine-18-FDG PET. J Nucl Med 1995; 36: 1238–18
  • Kuhl DE, Small GW, Riege WH. Cerebral metabolic patterns before the diagnosis of probable Alzheimer's disease [Abstract]. J Cereb Blood Flow Metab 1987; 7: S406, suppl
  • Haxby JV, Grady CL, Koss E, Horwitz B, Heston L, Schapiro M, et al. Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type. Arch Neurol 1990; 47: 753–60
  • Small GW, Mazziotta JC, Collins MT, Baxter LR, Phelps ME, Mandelkern MA, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease. JAMA 1995; 273: 942–7
  • Reiman EM, Caselli RJ, Yun LS, Chen K, Bandy D, Minoshima S, et al. Preclinical evidence of Alzheimer's disease in persons homozygous for the ϵ4 allele for apolipoprotein E. N Engl J Med 1996; 334: 752–8
  • Kumar A, Newberg A, Alavi A, Berlin J, Smith R, Reivich M. Regional cerebral glucose metabolism in late-life depression and Alzheimer disease: a preliminary positron emission tomography study. Proc Natl Acad Sci USA 1993; 90: 7019–23
  • Prohovnik I, Mayeux R, Sackeim HA, Smith G, Stern Y, Alderson PO. Cerebral perfusion as a diagnostic marker of early Alzheimer's disease. Neurology 1988; 38: 931–7
  • Schapiro MB, Pietrini P, Grady CL, Ball MJ, DeCarli C, Kumar A, et al. Reductions in parietal and temporal cerebral metabolic rates for glucose are not specific for Alzheimer's disease. J Neurol Neurosurg Psychiatry 1993; 56: 859–64
  • Rapoport SI. Anatomic and functional brain imaging in Alzheimer's disease. Psychopharmacology: the fourth generation of progress, FE Bloom, DJ Kupfer. Raven, New York 1995; 1401–15
  • Blass JP, Gibson GE. The role of oxidative abnormalities in the pathophysiology of Alzheimer's disease. Rev Neurol 1991; 147: 513–25
  • Blass JP, Gibson GE. Nonneural markers in Alzheimer disease. Alzheimer Dis Assoc Disord 1992; 6: 205–24
  • Pettegrew JW, McClure RJ, Kanfer JN, Mason RP, Panchalingam K, Klunk WE. The role of membranes and energetics in Alzheimer's disease. Alzheimer disease, RD Terry, R Katzman, KL Bick. Raven, New York 1994; 369–86
  • Bowen DM, Davison AN. Biochemical studies of nerve cells and energy metabolism in Alzheimer's disease. Br Med Bull 1986; 1: 75–80
  • Sorbi S, Mortilla M, Piacentini S, Tonini S, Amaducci L. Altered hexokinase activity in skin cultured fibroblasts and leukocytes from Alzheimer's disease patients. Neurosci Lett 1990; 117: 165–8
  • Kish SJ, Bergeron C, Rajput A, Dozic S, Mastrogiacomo F, Chang LJ, et al. Brain cytochrome oxidase in Alzheimer's disease. J Neurochem 1992; 59: 776–9
  • Simonian NA, Hyman BT. Functional alterations in Alzheimer's disease: diminution of cytochrome oxidase in the hippocampal formation. J Neuropathol Exp Neurol 1993; 52: 580–5
  • Parker WD. Cytochrome oxidase deficiency in Alzheimer's disease. Ann NY Acad Sci 1991; 640: 59–64
  • Brown GG, Levine SR, Gorell JM, Pettegrew JW, Gdowski JW, Bueri JA, et al. In vivo 31P NMR profiles of Alzheimer's disease and multiple subcortical infarct dementia. Neurology 1989; 39: 1423–7
  • Sparks DL, Hunsaker JC, III, Scheff SW, Kryscio RJ, Henson JL, Markesbery WR. Cortical senile plaques in coronary artery, disease, aging and Alzheimer's, disease. Neurobiol, Aging 1990; 11: 601–7
  • Aronson MK, Ooi WL, Morgenstern H, Hafne MS, Masur D, Crystal H. Women, myocardial infarction, and dementia in the very old. Neurology 1990; 40: 1102–6
  • Zubenko GS. Biological correlates of clinical heterogeneity in primary dementia. Neuropsychopharmacology 1992; 6: 77–93
  • Roth GS, Joseph JA, Mason RP. Membrane alterations as causes of impaired signal transduction in Alzheimer's disease and aging. Trends Neurosci 1995; 18: 203–6
  • Heron DS, Shinitzky M, Hershkowitz M, Samuel D. Lipid fluidity markedly modulates the binding of serotonin to mouse brain membrane. Proc Natl Acad Sci USA 1980; 77: 7463–7
  • Hershkowitz M, Heron D, Samuel D, Shinitzky M. The modulation of protein phosphorylation and receptor binding in synaptic membranes by changes in lipid fluidity: implications for ageing. Prog Brain Res 1982; 56: 419–34
  • McClure RJ, Kanfer JN, Panchalingam K, Klunk WE, Pettegrew JW. Alzheimer's disease: membrane-associated metabolic changes. Ann NY Acad Sci 1994; 747: 110–24
  • Klunk WE, McClure RJ, Pettegrew JW. l-Phosphoserine, a metabolite elevated in Alzheimer's disease, interacts with specific l-glutamate receptor subtypes. J Neurochem 1991; 56: 1997–2003
  • Andriamampandry C, Kanfer JN. Inhibition of cytosolic human forebrain choline acetyltransferase activity by phospho-l-serine: a phosphomonoester that accumulates during early stages of Alzheimer's disease. Neurobiol Aging 1993; 14: 367–72
  • Mason RP, Trumbore MV, Pettegrew JW. Membrane interactions of phosphomonoester elevated early in Alzheimer's disease. Neurobiol Aging 1995; 16: 531–9
  • Söderberg M, Edlund C, Alafuzoff I, Kristensson K, Dallner G. Lipid composition in different regions of the brain in Alzheimer's disease/senile dementia of Alzheimer's type. J Neurochem 1992; 59: 1646–53
  • Nakada T, Kwee IL, Ellis WG. Membrane fatty acid composition shows delta-6-desaturase abnormalities in Alzheimer's disease. Neuroreport 1990; 1: 153–5
  • Kwee IL, Nakada T, Ellis WG. Elevation in relative levels of brain membrane unsaturated fatty acids in Alzheimer's disease: high resolution proton spectroscopic studies of membrane lipid extracts. Magn Reson Med 1991; 21: 49–54
  • Söderberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer's disease. Lipids 1991; 26: 421–5
  • Mason RP, Shoemaker WJ, Shajenko L, Chambers TE, Herbette LG. Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol. Neurobiol Aging 1992; 13: 413–9
  • Shinitzky M, Barenholz Y. Fluidity parameters of lipid regions determined by fluorescence polarization. Biochim Biophys Acta 1978; 515: 367–94
  • Söderberg M, Edlund C, Kristensson K, Dallner G. Lipid compositions of different regions of the human brain during aging. J Neurochem 1990; 54: 415–23
  • Struck DK, Lennarz WJ. The function of saccharide-lipids in synthesis of glycoproteins. The biochemistry of glycoproteins and proteoglycans, WJ Lennarz. Plenum, New York 1980; 35–83
  • Emory CR, Ala TA, Frey WH, II. Ganglioside monoclonal antibody (A2B5) labels for Alzheimer's neurofibrillary tangles. Neurology 1987; 37: 768–72
  • Blennow K, Davidsson P, Wallin A, Fredman P, Gottfries CG, Karlsson I, et al. Gangliosides in cerebrospinal fluid in “probable Alzheimer's disease.”. Arch Neurol 1991; 48: 1032–5
  • Sweet RA, Zubenko GS. Peripheral markers in Alzheimer's disease. Dementia, A Burns, R Levy. Chapman & Hall, LondonEngland 1994; 387–403
  • Hicks N, Brammer MJ, Hymas N, Levy R. Platelet membrane properties in Alzheimer and multi-infarct dementias. Alzheimer Dis Assoc Disord 1987; 1: 90–7
  • Eagger S, Hajimohammadreza I, Fletcher K, Levy R, Brammer M. Platelet membrane, fluidity, family, history, and severity and age of onset in Alzheimer's, disease. Int J Geriatr, Psychiatry 1990; 5: 395–400
  • Hajimohammadreza I, Brammer MJ, Eagger S, Burns A, Levy R. Platelet and erythrocyte membrane changes in Alzheimer's disease. Biochim Biophys Acta 1990; 1025: 208–14
  • Piletz JE, Sarasua M, Whitehouse P, Chotani M. Intracellular membranes are more fluid in platelets of Alzheimer's disease patients. Neurobiol Aging 1991; 12: 401–6
  • Van Rensburg SJ, Carstens ME, Potocnik FCV, Aucamp AK, Taljaard JJF, Koch KR. Membrane fluidity of platelets and erythrocytes in patients with Alzheimer's disease and the effect of small amounts of aluminum on platelet and erythrocyte membranes. Neurochem Res 1992; 17: 825–9
  • Kálmán J, Dey I, Bona SV, Matkovics B, Brown D, Janka Z, et al. Platelet membrane fluidity and plasma malondialdehyde levels in Alzheimer's demented patients with and without family history of dementia. Biol Psychiatry 1994; 35: 190–4
  • Kaakkola S, Rosenberg PH, Alila A, Erkinjuntti T, Sulkava R, Palo J. Platelet membrane fluidity in Alzheimer's disease and multi-infarct dementia: a spin label study. Acta Neurol Scand 1991; 84: 18–21
  • Kukull WA, Hinds TR, Schellenberg GD, Van Belle G, Larson EB. Increased platelet membrane fluidity as a diagnostic marker for Alzheimer's disease: a test in population-based cases and controls. Neurology 1992; 42: 607–14
  • Zubenko GS, Cohen BM, Reynolds CF, Boller F, Malinakova I, Keefe N. Platelet membrane fluidity in Alzheimer's disease and major depression. Am J Psychiatry 1987; 144: 860–8
  • Zubenko GS, Wusylko M, Cohen BM, Boller F, Teply I. Family study of platelet membrane fluidity in Alzheimer's disease. Science 1987; 238: 539–42
  • Chakravarti A, Slaugenhaupt SA, Zubenko GS. Inheritance pattern of platelet membrane fluidity in Alzheimer disease. Am J Hum Genet 1989; 44: 799–805
  • Zubenko GS, Teply I. Longitudinal study of platelet membrane fluidity in Alzheimer's disease. Biol Psychiatry 1988; 24: 918–24
  • Zubenko GS, Huff FJ, Beyer J, Auerbach J, Teply I. Familial risk of dementia associated with a biologic subtype of Alzheimer's disease. Arch Gen Psychiatry 1988; 45: 889–93
  • Zubenko GS, Brenner RP, Teply I. Electroencephalographic correlates of increased platelet membrane fluidity in Alzheimer's disease. Arch Neurol 1988; 45: 1009–13
  • Zubenko GS, Brenner RP, Teply I. Risk factors for stroke and platelet membrane fluidity in Alzheimer's disease. Stroke 1991; 22: 997–1003
  • Zubenko GS, Huff FJ, Becker J, Beyer J, Teply I. Cognitive function and platelet membrane fluidity in Alzheimer's disease. Biol Psychiatry 1988; 24: 925–36
  • Zubenko GS, Teply I, Winwood E, Huff FJ, Moossy J, Sunderland T, et al. Prospective study of increased platelet membrane fluidity as a risk factor for Alzheimer's disease: results at five years. Am J Psychiatry 1996; 153: 420–3
  • Bush AI, Martins RN, Rumble B, Moir R, Fuller S, Milward E, et al. The amyloid precursor protein of Alzheimer's disease is released by human platelets. J Biol Chem 1990; 265: 15977–83
  • Cole GM, Galasko D, Shapiro IP, Saitoh T. Stimulated platelets release amyloid beta-protein precursor. Biochem Biophys Res Commun 1990; 170: 288–95
  • Schlossmacher MG, Ostaszewski BL, Hecker LI, Celi A, Haass C, Chin D, et al. Detection of distinct isoform patterns of the bˆ-amyloid precursor protein in human platelets and lymphocytes. Neurobiol Aging 1992; 13: 421–34
  • Di Luca M, Pastorino L, Cattabeni F, Zanardi R, Scarone S, Racagni G, et al. Abnormal pattern of platelet APP isoforms in Alzheimer disease and Down syndrome. Arch Neurol 1996; 53: 1162–6
  • Zubenko GS, Cohen BM, Boller F, Malinakova I, Keefe N, Chojnacki B. Platelet membrane abnormality in Alzheimer's disease. Ann Neurol 1987; 22: 237–44
  • Zubenko GS, Malinakova I, Chojnacki B. Proliferation of internal membranes in platelets from patients with Alzheimer's disease. J Neuropathol Exp Neurol 1987; 46: 407–18
  • Cohen BM, Zubenko GS, Babb S. Abnormal platelet membrane composition in Alzheimer's disease. Life Sci 1987; 40: 2445–51
  • Zubenko GS. Endoplasmic reticulum abnormality in Alzheimer's disease: selective alteration in platelet NADH-cytochrome C reductase activity. J Geriatr Psychiatry Neurol 1989; 2: 3–10
  • Haass C. Presenile because of presenilin: the presenilin genes and early onset Alzheimer's disease. Curr Opin Neurol 1996; 9: 254–9
  • Rozemuller JM, Eikelenboom P, Pals ST, Stam FC. Microglial cells around amyloid plaques in Alzheimer's disease express leucocyte adhesion molecules of the LFA-1 family. Neurosci Lett 1989; 101: 288–92
  • Banati RB, Gehrmann J, Schubert P, Kreutzberg GW. Cytotoxicity of microglia. Glia 1993; 7: 111–8
  • Giulian D. Reactive glia as rivals in regulating neuronal survival. Glia 1993; 7: 102–10
  • McGeer PL, Akiyama H, Itagaki S, McGeer EG. Immune system response in Alzheimer's disease. Can J Neurol Sci 1989; 16: 516–27, 4 suppl
  • Tooyama I, Kimura H, Akiyama H, McGeer PL. Reactive microglia express class I and class II major histocompatibility complex antigens in Alzheimer's disease. Brain Res 1990; 523: 273–80
  • Johnson SA, Lampert-Etchells M, Rozovsky I, Pasinetti GM, Finch CE. Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning. Neurobiol Aging 1992; 13: 641–8
  • Walker DG, McGeer PL. Complement gene expression in human brain: comparison between normal and Alzheimer disease cases. Mol Brain Res 1992; 14: 109–16
  • Rogers J, Cooper NR, Webster S, Schultz J, McGeer PL, Styren SD, et al. Complement activation by bˆ-amyloid in Alzheimer disease. Proc Natl Acad Sci USA 1992; 89: 10016–20
  • Jiang H, Burdick D, Glabe CG, Cotman CW, Tenner AJ. bˆ-Amyloid activates complement by binding to a specific region of the collagen-like domain in the Clq A chain. J Immunol 1994; 152: 5050–9
  • Murphy BF, Kirszbaum L, Walker ID, D'Apice AJF. SP-40, 40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis. J Clin Invest 1988; 81: 1858–64
  • Preissner KT, Podack ER, Müller-Eberhard HJ. SC5b-7, SC5b-8 and SC5b-9 complexes of complement: ultrastructure and localization of the S-protein (vitronectin) within the macromolecules. Eur J Immunol 1989; 19: 69–75
  • Rosse WF. Phosphatidylinositol-linked proteins and paroxysmal nocturnal hemoglobinuria. Blood 1990; 75: 1595–601
  • May PC, Lampert-Etchells M, Johnson SA, Poirier J, Masters JN, Finch CE. Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat. Neuron 1990; 5: 831–9
  • McGeer PL, Walker DG, Akiyama H, Kawamata T, Guan AL, Parker CJ, et al. Detection of the membrane inhibitor of reactive lysis (CD59) in diseased neurons of Alzheimer brain. Brain Res 1991; 544: 315–9
  • Breitner JCS, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, et al. Delayed onset of Alzheimer's disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging 1995; 16: 523–30
  • Breitner JCS, Gau BA, Welsh KA, Plassman BL, McDonald WM, Helms MJ, et al. Inverse association of anti-inflammatory treatments and Alzheimer's disease: initial results of a co-twin control study. Neurology 1994; 44: 227–32
  • Rich JB, Rasmusson DX, Folstein MF, Carson KA, Kawas C, Brandt J. Nonsteroidal anti-inflammatory drugs in Alzheimer's disease. Neurology 1995; 45: 51–5
  • Canadian Study of Health and Aging. Risk factors for Alzheimer's disease in Canada. Neurology 1994; 44: 2073–80
  • Andersen K, Launer LJ, Ott A, Hoes AW, Breteler MMB, Hofman A. Do nonsteroidal anti-inflammatory drugs decrease the risk for Alzheimer's disease? The Rotterdam study. Neurology 1995; 45: 1441–5
  • Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology 1993; 43: 1609–11
  • Prusiner SB. Molecular biology of prion diseases. Science 1991; 252: 1515–22
  • Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science 1982; 216: 136–44
  • DeArmond SJ, Prusiner SB. The neurochemistry of prion diseases. J Neurochem 1993; 61: 1589–601
  • Taraboulos A, Raeber AJ, Borchelt DR, Serban D, Prusiner SB. Synthesis and trafficking of prion proteins in cultured cells. Mol Biol Cell 1992; 3: 851–63
  • Borchelt DR, Taraboulos A, Prusiner SB. Evidence for synthesis of scrapie prion proteins in the endocytic pathway. J Biol Chem 1992; 267: 6188–99
  • Cohen FE, Pan KM, Huang Z, Baldwin M, Fletterick RJ, Prusiner SB. Structural clues to prion replication. Science 1994; 264: 530–1
  • Ghetti B, Tagliavini F, Masters CL, Beyreuther K, Giaccone G, Verga L, et al. Gerstmann-Sträussler-Scheinker, disease, II: Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected, family. Neurology 1989; 39: 1453–61
  • Giaccone G, Tagliavini F, Verga L, Frangione B, Farlow MR, Bugiani O, et al. Neurofibrillary tangles of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease share antigenic determinants with those of Alzheimer's disease. Brain Res 1990; 530: 325–9
  • Tagliavini F, Prelli F, Ghisto J, Bugiani O, Serban D, Prusiner SB, et al. Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana kindred) is an 11-kd fragment of prion protein with an N-terminal glycine at codon 58. EMBO J 1991; 10: 513–9
  • Hsiao K, Dloughy SR, Farlow MR, Cass C, Da Costa M, Conneally PM, et al. Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles. Nat Genet 1992; 1: 68–71
  • Rifat SL, Eastwood MR. The role of aluminum in dementia of Alzheimer's type: a review of the hypotheses and summary of the evidence. Dementia, A Burns, R Levy. Chapman & Hall, LondonEngland 1994; 268–80
  • Alfrey AC, LeGendre GR, Kaehny WD. The dialysis encephalopathy syndrome: possible aluminum intoxication. N Engl J Med 1976; 294: 184–8
  • Platts MM, Goode GC, Hislop JS. Composition of the domestic water supply and the incidence of fractures and encephalopathy in patients on home dialysis. Br Med J 1977; 2: 657–60
  • McDermott JR, Smith AI, Ward MK, Parkinson IS, Kerr DN. Brain-aluminum concentration in dialysis encephalopathy. Lancet 1978; 1: 901–4
  • Crapper DR, Quittkat S, Krishnan SS, Dalton AJ, De Boni U. Intranuclear aluminum content in Alzheimer's, disease, dialysis, encephalopathy, and experimental aluminum, encephalopathy. Acta Neuropathol, (Berl) 1980; 50: 19–24
  • Alfrey AC. Systemic toxicity of aluminum in man. Neurobiol Aging 1986; 7: 543–4
  • Spofforth J. Cases of aluminum poisoning [Letter]. Lancet 1921; 1: 1301
  • MacLaughlin AIG, Kazantzis G, King E. Pulmonary fibrosis and encephalopathy associated with the inhalation of aluminum dust. Br J Ind Med 1962; 19: 253–63
  • Longstreth WT, Rosenstock L, Heyer NJ. Potroom palsy? Neurologic disorder in three aluminum smelter workers. Arch Intern Med 1985; 145: 1972–5
  • Kobayashi S, Hirota N, Saito K, Utsuyama M. Aluminum accumulation in tangle-bearing neurons of Alzheimer's disease with Balint's syndrome in a long-term aluminum refiner. Acta Neuropathol (Berl) 1987; 74: 47–52
  • Crapper DR, Krishnan SS, Dalton AJ. Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science 1973; 180: 511–3
  • Duckett S, Galle P. Electron microscope-microprobe studies of aluminum in the brains of cases of Alzheimer's disease and aging patients [Abstract]. J Neuropathol Exp Neurol 1980; 39: 350
  • Perl DP, Brody AR. Alzheimer's disease: x-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science 1980; 208: 297–9
  • Candy JM, Oakley AE, Klinowski J, Carpenter TA, Perry RH, Atack JR, et al. Aluminosilicates and senile plaque formation in Alzheimer's disease. Lancet 1986; 1: 354–7
  • Ghetti B, Bugiani O. 'Aluminum's disease' and Alzheimer's disease. Neurobiol Aging 1986; 7: 536–7
  • Wisniewski HM. No evidence for aluminum in etiology and pathogenesis of Alzheimer's disease. Neurobiol Aging 1986; 7: 532–5
  • Crapper McLachlan DR, Dalton AJ, Kruck TPA, Bell MY, Smith WL, Kalow W, et al. Intramuscular desferrioxamine in patients with Alzheimer's disease. Lancet 1991; 337: 1304–8
  • Elsworth JD, Deutch AY, Redmond DE, Jr, Taylor JR, Sladek JR, Jr, Roth RH. Symptomatic and asymptomatic, 1-methyl-4-phenyl-12,3,6-tetrahydropyridine-treated primates: biochemical changes in striatal regions. Neuroscience 1989; 33: 323–31
  • Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979–80
  • Tanner CM, Langston JW. Do environmental toxins cause Parkinson's disease? A critical review. Neurology 1990; 40: 17–30
  • Steventon GB, Heafield MTE, Waring RH, Williams AC. Xenobiotic metabolism in Parkinson's disease. Neurology 1989; 39: 883–7
  • Heikkila RE, Manzino L, Cabbat FS, Duvoisin RC. Protection against the dopaminergic neurotoxicity of, 1-methyl-4-phenyl-12,5,6-tetrahydropyridine by monoamine oxidase inhibitors. Nature 1984; 311: 467–9
  • Golbe JI. Deprenyl as symptomatic therapy in Parkinson's disease. Clin Neuropharmacol 1988; 11: 387–400
  • Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1989; 321: 1364–71
  • Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med 1993; 328: 176–83
  • Elizan TS, Moros DA, Yahr MD. Early combination of selegiline and low-dose levodopa as initial symptomatic therapy in Parkinson's disease: experience in 26 patients receiving combined therapy for 26 months. Arch Neurol 1991; 48: 31–4
  • Plaitakis A, Shashidharan P. Amyotrophic lateral, sclerosisglutamate, and oxidative stress. Psychopharmacology: the fourth generation of progress, FE Bloom, DJ Kupfer. Raven, New York 1995; 1531–43
  • Rosen DR. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis [Erratum]. Nature 1993; 364: 362
  • Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, et al. Amyotrophic lateral sclerosis and structural defects in, Cu, Zn superoxide, dismutase. Science 1993; 261: 1047–51
  • Mourelatos Z, Yachnis A, Rorke L, Mikol J, Gonatas NK. The Golgi apparatus of motor neurons in amyotrophic lateral sclerosis. Ann Neurol 1993; 33: 608–15
  • Hirano A, Kurland LT, Krooth RS, Lessel S. Parkinsonism-dementia, complex, an endemic disease on the island of, Guam. Brain 1961; 84: 642–79
  • Spencer PS, Nunn PB, Hugon J, Ludolph AC, Ross SM, Roy DN, et al. Guam amyotrophic lateral sclerosis-parkinsonism–dementia linked to a plant excitant neurotoxin. Science 1987; 237: 517–22
  • Garruto RM, Yanagihara R, Gajdusek DC. Cycads and amyotrophic lateral sclerosis/parkinsonism-dementia [Letter]. Lancet 1988; 2: 1079
  • Duncan MW, Steele JC, Kopin IJ, Markey SP. 2-Amino-3-(methylamino)-propanoic acid (BMAA) in cycad flour: an unlikely cause of amyotrophic lateral sclerosis and parkinsonism-dementia of Guam. Neurology 1990; 40: 767–72
  • Zubenko GS, Stiffler S, Kopp U, Hughes H, Kaplan BB, Moossy J. Lack of variation in the nucleotide sequence corresponding to the transmembrane domain of the bˆ-amyloid precursor protein in Alzheimer's disease. Am J Med Genet Neuropsychiatr Genet 1993; 48: 131–6
  • Schellenberg GD. Progress in Alzheimer's disease genetics. Curr Opin Neurol 1995; 8: 262–7
  • Sisodia SS, Price DL. Role of the bˆ-amyloid protein in Alzheimer's disease. FASEB J 1995; 9: 366–70
  • Schellenberg GD, Bird TD, Wijsman EM, Orr HT, Anderson L, Nemens E, et al. Genetic linkage evidence for a familial Alzheimer's disease locus on chromosome 14. Science 1992; 258: 668–71
  • Campion D, Flaman JM, Brice A, Hannequin D, Dubois B, Martin C, et al. Mutations of the presenilin I gene in families with early-onset Alzheimer's disease. Hum Mol Genet 1995; 4: 2373–7
  • Alzheimer's Disease Collaborative Group. The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families [Letter]. Nat Genet 1995; 11: 219–22
  • Cruts M, Backhovens H, Wang SY, Gassen GV, Theuns J, De Jonghe C, et al. Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24. 3. Hum Mol Genet 1995; 4: 2363–71
  • Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikdea M, et al. Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 1995; 375: 754–60
  • Levy-Lahad E, Wijsman EM, Nemens E, Anderson L, Goddard KAB, Weber JLJ, et al. A familial Alzheimer's disease locus on chromosome 1. Science 1995; 269: 970–2
  • Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, et al. Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Science 1995; 269: 973–7
  • Holland AJ. Down's syndrome and dementia of the Alzheimer type. Dementia, A Burns, R Levy. Chapman & Hall, LondonEngland 1994; 695–708
  • Chartier-Harlin MC, Crawford F, Houlden H, Warren A, Hughes D, Fidani L, et al. Early-onset Alzheimer's disease caused by mutations at codon 717 of the bˆ-amyloid precursor protein gene. Nature 1991; 353: 844–6
  • Goate AM, Chartier-Harlin CM, Mullan M, Brown J, Crawford F, Fidani L, et al. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 1991; 349: 704–6
  • Murrell J, Farlow M, Ghetti B, Benson MD. A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 1991; 254: 97–9
  • Mullan M, Crawford F, Axelman K, Houlden H, Lilius L, Winblad B, et al. A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of bˆ-amyloid. Nat Genet 1992; 1: 345–7
  • Hendriks L, Van Duijn CM, Cras P, Cruts M, Van Hul W, Van Harskamp F, et al. Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the bˆ-amyloid precursor protein gene. Nat Genet 1992; 1: 218–21
  • Levy E, Carman MD, Fernandez-Madrid JJ, Power MD, Lieberburg I, Van Duinen SG, et al. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral, hemorrhage, Dutch, type. Science 1990; 248: 1124–6
  • Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F bˆ-amyloid precursor protein. Nature 1995; 373: 523–7
  • Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, et al. Correlative memory, deficits, Abˆ, elevation, and amyloid plaques in transgenic, mice. Science 1996; 274: 99–102
  • Price DL, Sisodia SS. Cellular and molecular biology of Alzheimer's disease and animal models. Annu Rev Med 1994; 45: 435–46
  • Tanzi RE, Vaula G, Romano DM, Vaula G, Romano DM, Mortilla M, et al. Assessment of amyloid bˆ-protein precursor gene mutations in a large set of familial and sporadic Alzheimer disease cases. Am J Hum Genet 1992; 51: 273–82
  • St George-Hyslop P, Haines J, Rogaev E, Mortilla M, Vaula G, Pericak-Vance M, et al. Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14. Nat Genet 1992; 2: 330–4
  • Van Broeckhoven C, Backhovens H, Cruts M, De Winter G, Bruyland M, Cras P, et al. Mapping of a gene predisposing to early-onset Alzheimer's disease to chromosome 14q24. 3. Nat Genet 1992; 2: 335–9
  • Nechiporuk A, Fain P, Kort E, Nee LE, Frommelt E, Polinsky RJ, et al. Linkage of familial Alzheimer disease to chromo some 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores. Am J Med Genet 1993; 48: 63–6
  • Sahara N, Yahagi Y, Takagi H, Kondo T, Okochi M, Usami M, et al. Identification and characterization of presenilin, I-467, I-463 and, I-374. FEBS, Lett 1996; 381: 7–11
  • Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 1995; 376: 775–8
  • Levitan D, Greenwald I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene [Letter]. Nature 1995; 377: 351–4
  • Wolozin B, Iwasaki K, Vito P, Ganjei JK, Lacana E, Sunderland T, et al. Participation of presenilin 2 in apoptosis: enhanced basal activity conferred by an Alzheimer mutation. Science 1996; 274: 1710–3
  • Yamatsuji T, Matsui T, Okamoto T, Komatsuzaki K, Takeda S, Fukumoto H, et al. G protein–mediated neuronal DNA fragmentation induced by familial Alzheimer's disease–associated mutants of APP. Science 1996; 272: 1349–52
  • Yamatsuji T, Okamoto T, Takeda S, Murayama Y, Tanaka N, Nishimoto I. Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype. EMBO J 1996; 15: 498–509
  • Pericak-Vance MA, Haines JL. Genetic susceptibility to Alzheimer disease. Trends Genet 1995; 11: 504–8
  • Pericak-Vance MA, Bebout JL, Gaskell PC, Jr, Yamaoka LH, Hung WY, Alberts MJ, et al. Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am J Hum Genet 1991; 48: 1034–50
  • Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, et al. Gene dose of apolipoprotein E type-4 allele and the risk of Alzheimer's disease in late onset families. Science 1993; 261: 921–3
  • Saunders AM, Strittmatter WJ, Schmechel D, St George-Hyslop PH, Pericak-Vance MA, Joo SH, et al. Association of apolipoprotein E allele ϵ4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993; 43: 1467–72
  • Menzel HJ, Kladetzky RG, Assmann G. Apolipoprotein E polymorphism and coronary artery disease. Arteriosclerosis 1983; 3: 310–5
  • Noguchi S, Murakami K, Yamada N. Apolipoprotein E genotype and Alzheimer's disease [Letter]. Lancet 1993; 342: 737
  • Ueki A, Kawano M, Namba Y, Kawakami M, Ikeda K. A high frequency of apolipoprotein E4 isoprotein in Japanese patients with late-onset nonfamilial Alzheimer's disease. Neurosci Lett 1993; 163: 166–8
  • Chartier-Harlin MC, Parfitt M, Legrain S, Pérez-Tur J, Brousseau T, Evans A, et al. Apolipoprotein, E, ϵ4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the, 19q13., 2 chromosomal, region. Hum Mol, Genet 1994; 3: 569–74
  • Dai XY, Nanko S, Hattori M, Fukuda R, Nagata K, Isse K, et al. Association of apolipoprotein E4 with sporadic Alzheimer's disease is more pronounced in early onset type. Neurosci Lett 1994; 175: 74–76
  • Yoshizawa T, Yamakawa-Kobayashi K, Komatsuzaki Y, Arinami T, Oguni E, Mizusawa H, et al. Dose-dependent association of apolipoprotein E allele ϵ4 with, late-onset, sporadic Alzheimer's, disease. Ann Neurol 1994; 36: 656–9
  • Zubenko GS, Stiffler S, Stabler S, Kopp U, Hughes HB, Cohen BM, et al. Association of the apolipoprotein E ϵ4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease. Am J Med Genet Neuropsychiatr Genet 1994; 54: 199–205
  • Hendrie HC, Hall KS, Hui S, Unverzagt FW, Yu CE, Lahiri DK, et al. Apolipoprotein E genotypes and Alzheimer's disease in a community study of elderly African Americans. Ann Neurol 1995; 37: 118–20
  • Kamboh MI. Apolipoprotein E polymorphism and susceptibility to Alzheimer's disease. Hum Biol 1995; 67: 195–215
  • Maestre G, Ottman R, Stern Y, Gurland B, Chun M, Tang MX, et al. Apolipoprotein E and Alzheimer's disease: ethnic variation in genotypic risks. Ann Neurol 1995; 37: 254–9
  • Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC, Jr, et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer's disease. Nat Genet 1994; 7: 180–4
  • Cumming AM, Robertson FW. Polymorphism at the apoprotein-E locus in relation to risk of coronary disease. Clin Genet 1984; 25: 310–3
  • Lenzen HJ, Assmann G, Buchwalsky R, Schulte H. Association of apolipoprotein E, polymorphism, low-density lipoprotein, cholesterol, and coronary artery, disease. Clin, Chem 1986; 32: 778–81
  • Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988; 8: 1–21
  • Van Bockxmeer FM, Mamotte CDS. Apolipoprotein ϵ4 homozygosity in young men with coronary heart disease. Lancet 1992; 340: 879–80
  • Eichner JE, Kuller LH, Orchard TJ, Grandits GA, McCallum LM, Ferrell RE, et al. Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease. Am J Cardiol 1993; 71: 160–5
  • Marder K, Maestre G, Cote L, Mejia H, Alfaro B, Halim A, et al. The apolipoprotein ϵ4 allele in Parkinson's disease with and without dementia. Neurology 1994; 44: 1330–1
  • Pickering-Brown SM, Mann DM, Bourke JP, Roberts DA, Balderson D, Burns A, et al. Apolipoprotein E4 and Alzheimer's disease pathology in Lewy body disease and in other beta-amyloid-forming diseases [Letter]. Lancet 1994; 343: 1155
  • Roller WC, Glatt SL, Hubble JP, Paolo A, Troster AI, Handler MS, et al. Apolipoprotein E genotypes in Parkinson's disease with and without dementia. Ann Neurol 1995; 37: 242–5
  • Arai H, Higuchi S, Muramatsu T, Iwatsubo T, Sasaki H, Trojanowski JQ. Apolipoprotein E gene in diffuse Lewy body disease with or without co-existing Alzheimer's disease [Letter]. Lancet 1994; 334: 1307
  • Galasko D, Saitoh T, Xia Y, Thal LJ, Katzman R, Hill LT, et al. The apolipoprotein E allele ϵ4 is over-represented in patients with the Lewy body variant of Alzheimer's disease. Neurology 1994; 44: 1950–1
  • Harrington CR, Louwagie J, Rossau R, Vanmechelen E, Perry RH, Perry EK, et al. Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types: significance for etiological theories of Alzheimer's disease. Am J Pathol 1994; 145: 1472–84
  • St Clair D, Norrman J, Perry R, Yates C, Wilcock G, Brookes A. Apolipoprotein E ϵ4 allele frequency in patients with Lewy body, dementia, Alzheimer's disease and age-matched, controls. Neurosci, Lett 1994; 176: 45–6
  • Lippa CF, Smith TW, Saunders AM, Crook R, Pulaski-Salo D, Davies P, et al. Apolipoprotein E genotype and Lewy body disease. Neurology 1995; 45: 97–103
  • Krishnan KRR, Ritchie JC, Jr, Tupler LA, McDonald WM, Knight D, Nemeroff CB. Apolipoprotein E ϵ4.[Letter]. Neurology 1994; 44: 2420–1
  • Zubenko GS, Henderson R, Stiffler JS, Stabler S, Rosen J, Kaplan BB. Association of the APOE ϵ4 allele with clinical subtypes of late life depression. Biol Psychiatry 1996; 40: 1008–16
  • Okuizumi K, Onodera O, Tanaka H, Kobayashi H, Tsuji S, Takahashi H, et al. ApoE-epsilon 4 and early-onset Alzheimer's [Letter]. Nat Genet 1994; 7: 10–11
  • Van Duijn CM, De Knijff P, Cruts M, Wehnert A, Havekes LM, Hofman A, et al. Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease. Nat Genet 1994; 7: 74–8
  • Schächter F, Faure-Delanef L, Guénot F, Rouger H, Froguel P, Lesueur-Ginot L, et al. Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 1994; 6: 29–32
  • Payami H, Montee KR, Kaye JA, Bird TD, Yu CE, Wijsman EM, et al. Alzheimer's, disease, apolipoprotein, ϵ4, and gender, [Letter]. JAMA 1994; 271: 1316–7
  • Payami H, Zareparsi S, Montee KR, Sexton GJ, Kaye JA, Bird TD, et al. Gender difference in apolipoprotein E-associated risk for familial Alzheimer disease: a possible clue to the higher incidence of Alzheimer disease in women. Am J Hum Genet 1996; 58: 803–1
  • Mayeux R, Ottman R, Maestre G, Ngai C, Tang MX, Ginsberg H, et al. Synergistic effects of traumatic head injury and apolipoprotein-ϵ4 in patients with Alzheimer's disease. Neurology 1995; 45: 555–7
  • Petersen RC, Smith GE, Ivnik RJ, Tangalos EG, Schaid DJ, Thibodeau SN, et al. Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA 1995; 273: 1274–8
  • Wisniewski T, Frangione B. Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid. Neurosci Lett 1992; 135: 235–8
  • LaDu MJ, Falduto MT, Manelli AM, Reardon CA, Getz GS, Frail DE. Isoform-specific binding of apolipoprotein E to beta-amyloid. J Biol Chem 1994; 269: 23403–6
  • Ma J, Yee A, Brewer HB, Jr, Das S, Potter H. Amyloid-associated proteins alpha 1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer beta-protein into filaments. Nature 1994; 372: 92–4
  • Rebeck GW, Reiter JS, Strickland DK, Hyman BT. Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions. Neuron 1993; 11: 575–80
  • Schmechel DE, Saunders AM, Strittmatter WJ, Crain BJ, Hulette CM, Joo SH, et al. Increased amyloid bˆ-peptide deposition in cerebral cortex as a consequence of apolipoprotein E genotype in late-onset Alzheimer disease. Proc Natl Acad Sci USA 1993; 90: 9649–53
  • Kounnas MZ, Moir RD, Rebeck GW, Bush Al, Argraves WS, Tanzi RE, et al. LDL receptor-related, protein, a multifunctional ApoE, receptor, binds secreted bˆ-amyloid precursor protein and mediates its, degradation. Cell 1995; 82: 331–40
  • Strittmatter WJ, Saunders AM, Goedert M, Weisgraber KH, Dong LM, Jakes R, et al. Isoform-specific interactions of apolipoprotein E with microtubule-associated protein tau: implications for Alzheimer disease. Proc Natl Acad Sci USA 1994; 91: 11183–6
  • Strittmatter WJ, Weisgraber KH, Goedert M, Saunders AM, Huang D, Corder EH, et al. Hypothesis: microtubule instability and paired helical filament formation in the Alzheimer disease brain are related to apolipoprotein E genotype. Exp Neurol 1994; 125: 163–71
  • Poirier J. Apolipoprotein E in animal models of CNS injury and in Alzheimer's disease. Trends Neurosci 1994; 17: 525–30
  • Nathan BP, Bellosta S, Sanan DA, Weisgraber KH, Mahley RW, Pitas RE. Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro. Science 1994; 264: 850–2
  • Roses AD, Devlin B, Conneally PM, Small GW, Saunders AM, Pritchard M, et al. Measuring the genetic contributions of APOE in late-onset Alzheimer's disease [Abstract]. Am J Hum Genet 1995; 57: A202, suppl
  • Kamboh MI, Sanghera DK, Ferrell RE, DeKosky ST. APOE*4-associated Alzheimer's disease risk is modified by â1-antichymotrypsin polymorphism. Nat Genet 1995; 10: 486–8
  • Haines JL, Pritchard ML, Saunders AM, Schildkraut JM, Growdon JH, Gaskell PC, et al. No genetic effect of â1-antichymotrypsin in Alzheimer disease. Genomics 1996; 33: 53–6
  • Murphy GM, Jr, Sullivan EV, Gallagher-Thompson D, Thompson LW, Van Duijn CM, Forno LS, et al. No association between the alpha 1–antichymotrypsin A allele and Alzheimer's disease. Neurology 1997; 48: 1313–6
  • Zubenko GS, Stiffler JS, Hughes HB, Hurtt MR. Identification of a putative Alzheimer's disease risk locus on the X-chromosome [Abstract]. Presented at the tenth annual meeting of the American Association for Geriatric Psychiatry. Orlando, Florida March, 1997
  • Chen X, Xia Y, Alford M, DeTeresa R, Hansen L, Klauber MR, et al. The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer's disease. Ann Neurol 1995; 38: 653–8
  • Saitoh T, Xia Y, Chen X, Masliah E, Galasko D, Shults C, et al. The CYP2D6B mutant allele is overrepresented in the Lewy body variant of Alzheimer's disease. Ann Neurol 1995; 37: 110–2
  • Berg L, Miller JP, Storandt M, Duchek J, Morris JC, Rubin EH, et al. Mild senile dementia of the Alzheimer, type, 2: longitudinal, assessment. Ann Neurol 1988; 23: 477–84
  • Van Dijk PTM, Dippel DWJ, Habbema JDF. Survival of patients with dementia. J Am Geriatr Soc 1991; 39: 603–10

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