Advanced search
Publication Cover
Expert Review of Neurotherapeutics Volume 10, 2010 - Issue 5
Submit an article Journal homepage
104
Views
47
CrossRef citations to date
0
Altmetric
Review

Causes versus effects: the increasing complexities of Alzheimer’s disease pathogenesis

Siddhartha Mondragón-Rodríguez Département de Physiologie, Université de Montréal, Québec, Canada; Département de Physiologie, Université de Montréal, Québec, Canada
,
Gustavo Basurto-Islas Département de Physiologie, Université de Montréal, Québec, Canada; Département de Physiologie, Université de Montréal, Québec, Canada
,
Hyoung-gon Lee Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA; Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
,
George Perry Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA; College of Sciences, University of Texas at San Antonio, TX, USA; Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA; College of Sciences, University of Texas at San Antonio, TX, USA
,
Xiongwei Zhu Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA; Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA
,
Rudy J Castellani Department of Pathology, University of Maryland, MD, USA; Department of Pathology, University of Maryland, MD, USA
&
Mark A Smith Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA;[email protected]
 show all
Pages 683-691 | Published online: 09 Jan 2014

References

  • Zekanowski C, Styczynska M, Peplonska B et al. Mutations in presenilin 1, presenilin 2 and amyloid precursor protein genes in patients with early-onset Alzheimer’s disease in Poland. Exp. Neurol.184(2), 991–996 (2003).
  • Zekanowski C, Religa D, Graff C, Filipek S, Kuznicki J. Genetic aspects of Alzheimer’s disease. Acta Neurobiol. Exp. (Wars.)64(1), 19–31 (2004).
  • Zawia NH, Lahiri DK, Cardozo-Pelaez F. Epigenetics, oxidative stress, and Alzheimer disease. Free Radic. Biol. Med.46(9), 1241–1249 (2009).
  • Smith MA, Nunomura A, Zhu X, Takeda A, Perry G. Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease. Antioxid. Redox Signal.2(3), 413–420 (2000).
  • Rapoport SI, Horwitz B, Grady CL, Haxby JV, DeCarli C, Schapiro MB. Aβnormal brain glucose metabolism in Alzheimer’s disease, as measured by position emission tomography. Adv. Exp. Med. Biol.29(1), 231–248 (1991).
  • Matsuda H. Cerebral blood flow and metabolic abnormalities in Alzheimer’s disease. Ann. Nucl. Med.15(2), 85–92 (2001).
  • Blass JP. Cerebrometabolic abnormalities in Alzheimer’s disease. Neurol. Res.25(6), 556–566 (2003).
  • Ackl N, Ising M, Schreiber YA, Atiya M, Sonntag A, Auer DP. Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer’s disease. Neurosci. Lett.384(1–2), 23–28 (2005).
  • Webber KM, Raina AK, Marlatt MW et al. The cell cycle in Alzheimer disease: a unique target for neuropharmacology. Mech. Ageing Dev.126(10), 1019–1025 (2005).
  • Woods J, Snape M, Smith MA. The cell cycle hypothesis of Alzheimer’s disease: suggestions for drug development. Biochim. Biophys. Acta1772(4), 503–508 (2007).
  • Lee KW, Kim JB, Seo JS et al. Behavioral stress accelerates plaque pathogenesis in the brain of Tg2576 mice via generation of metabolic oxidative stress. J. Neurochem.108(1), 165–175 (2009).
  • Ma YS, Wu SB, Lee WY, Cheng JS, Wei YH. Response to the increase of oxidative stress and mutation of mitochondrial DNA in aging. Biochim. Biophys. Acta1790(10), 1021–1029 (2009).
  • Gabbita SP, Lovell MA, Markesbery WR. Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J. Neurochem.71(5), 2034–2040 (1998).
  • Kadioglu E, Sardas S, Aslan S, Isik E, Esat Karakaya A. Detection of oxidative DNA damage in lymphocytes of patients with Alzheimer’s disease. Biomarkers9(2), 203–209 (2004).
  • Lovell MA, Markesbery WR. Oxidatively modified RNA in mild cognitive impairment. Neurobiol. Dis.29(2), 169–175 (2008).
  • Kovacech B, Zilka N, Novak M. New age of neuroproteomics in Alzheimer’s disease research. Cell. Mol. Neurobiol.29(6–7), 799–805 (2009).
  • Ghoshal N, Garcia-Sierra F, Wuu J et al. Tau conformational changes correspond to impairments of episodic memory in mild cognitive impairment and Alzheimer’s disease. Exp. Neurol.177(2), 475–493 (2002).
  • Gamblin TC, Chen F, Zambrano A et al. Caspase cleavage of tau: linking amyloid and neurofibrillary tangles in Alzheimer’s disease. Proc. Natl Acad. Sci. USA100(17), 10032–10037 (2003).
  • Biernat J, Gustke N, Drewes G, Mandelkow EM, Mandelkow E. Phosphorylation of Ser262 strongly reduces binding of tau to microtubules, distinction between PHF-like immunoreactivity and microtubule binding. Neuron11(1), 153–163 (1993).
  • Alonso A, Zaidi T, Novak M, Grundke-Iqbal I, Iqbal K. Hyperphosphorylation induces self-assembly of tau into tangles of paired helical filaments/straight filaments. Proc. Natl Acad. Sci. USA98(12), 6923–6928 (2001).
  • Avila J. Tau phosphorylation and aggregation in Alzheimer’s disease pathology. FEBS Lett.580(12), 2922–2927 (2006).
  • Di Fede G, Catania M, Morbin M et al. A recessive mutation in the APP gene with dominant-negative effect on amyloidogenesis. Science323(5920), 1473–1477 (2009).
  • Bernardi L, Geracitano S, Colao R et al. AβPP A713T mutation in late onset Alzheimer's disease with cerebrovascular lesions. J. Alzheimers Dis.17(2), 383–389 (2009).
  • Larner AJ, Doran M. Genotype–phenotype relationships of presenilin-1 mutations in Alzheimer’s disease: an update. J. Alzheimers Dis.17(2), 259–265 (2009).
  • Aleshkov S, Abraham CR, Zannis VI. Interaction of nascent ApoE2, ApoE3, and ApoE4 isoforms expressed in mammalian cells with amyloid peptide β1–40. Relevance to Alzheimer's disease. Biochemistry36(34), 10571–10580 (1997).
  • Adalbert R, Gilley J, Coleman MP. Aβ, tau and ApoE4 in Alzheimer’s disease, the axonal connection. Trends Mol. Med.13(4), 135–142 (2007).
  • Bu G. Apolipoprotein E and its receptors in Alzheimer’s disease: pathways, pathogenesis and therapy. Nat. Rev. Neurosci.10(5), 333–344 (2009).
  • Aggarwal NT, Wilson RS, Beck TL, Bienias JL, Berry-Kravis E, Bennett DA. The apolipoprotein E ε4 allele and incident Alzheimer’s disease in persons with mild cognitive impairment. Neurocase11(1), 3–7 (2005).
  • Adroer R, Santacruz P, Blesa R, Lopez-Pousa S, Ascaso C, Oliva R. Apolipoprotein E4 allele frequency in Spanish Alzheimer and control cases. Neurosci. Lett.189(3), 182–186 (1995).
  • Zurutuza L, Verpillat P, Raux G et al. APOE promoter polymorphisms do not confer independent risk for Alzheimer‘s disease in a French population. Eur. J. Hum. Genet.8(9), 713–716 (2000).
  • Vazquez-Higuera JL, Mateo I, Sanchez-Juan P et al. Genetic interaction between tau and the apolipoprotein E receptor LRP1 increases Alzheimer’s disease risk. Dement. Geriatr. Cogn. Disord.28(2), 116–120 (2009).
  • Zhong N, Weisgraber KH. Understanding the basis for the association of apoE4 with Alzheimer’s disease: opening the door for therapeutic approaches. Curr. Alzheimer Res.6(5), 415–418 (2009).
  • Batelli S, Albani D, Prato F et al. Early-onset Alzheimer disease in an Italian family with presenilin-1 double mutation E318G and G394V. Alzheimer Dis. Assoc. Disord.22(2), 184–187 (2008).
  • Brouwers N, Sleegers K, Van Broeckhoven C. Molecular genetics of Alzheimer’s disease: an update. Ann. Med.40(8), 562–583 (2008).
  • Lindquist SG, Hasholt L, Bahl JM et al. A novel presenilin 2 mutation (V393M) in early-onset dementia with profound language impairment. Eur. J. Neurol.15(10), 1135–1139 (2008).
  • Martinez-Garcia A, Aldudo J, Recuero M et al. Presenilin 1 polymorphism associated with Alzheimer’s disease in apolipoprotein E4 carriers. Dement. Geriatr. Cogn. Disord.26(5), 440–444 (2008).
  • de Bot ST, Kremer HP, Dooijes D, Verbeek MM. CSF studies facilitate DNA diagnosis in familial Alzheimer’s disease due to a presenilin-1 mutation. J. Alzheimers Dis.17(1), 53–57 (2009).
  • Hernandez-Santoyo A, Del Pozo Yauner L, Fuentes-Silva D et al. A single mutation at the sheet switch region results in conformational changes favoring l6 light-chain fibrillogenesis. J. Mol. Biol.396(2), 280–292 (2010).
  • Jansen C, Parchi P, Capellari S et al. Prion protein amyloidosis with divergent phenotype associated with two novel nonsense mutations in PRNP. Acta Neuropathol.119(2), 189–197 (2009).
  • Kowalska A. [The genetics of dementias. Part 1: molecular basis of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)]. Postepy Hig. Med. Dosw. (Online)63, 278–286 (2009).
  • Sadik G, Tanaka T, Kato K, Yanagi K, Kudo T, Takeda M. Differential interaction and aggregation of 3-repeat and 4-repeat tau isoforms with 14-13-3z protein. Biochem. Biophys. Res. Commun.383(1), 37–41 (2009).
  • Espinoza M, de Silva R, Dickson DW, Davies P. Differential incorporation of tau isoforms in Alzheimer’s disease. J. Alzheimers Dis.14(1), 1–16 (2008).
  • Avramopoulos D. Genetics of Alzheimer’s disease: recent advances. Genome Med.1(3), 34 (2009).
  • Liang X, Schnetz-Boutaud N, Kenealy SJ et al. Covariate analysis of late-onset Alzheimer disease refines the chromosome 12 locus. Mol. Psychiatry11(3), 280–285 (2006).
  • Lee HG, Casadesus G, Zhu X, Joseph JA, Perry G, Smith MA. Perspectives on the amyloid-β cascade hypothesis. J. Alzheimers Dis.6(2), 137–145 (2004).
  • Lee HG, Castellani RJ, Zhu X, Perry G, Smith MA. Amyloid-β in Alzheimer's disease: the horse or the cart? Pathogenic or protective? Int. J. Exp. Pathol.86(3), 133–138 (2005).
  • Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science297(5580), 353–356 (2002).
  • Sato N, Imaizumi K, Manabe T et al. Increased production of β-amyloid and vulnerability to endoplasmic reticulum stress by an aberrant spliced form of presenilin 2. J. Biol. Chem.276(3), 2108–2114 (2001).
  • Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ. Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and γ-secretase activity. Nature398(6727), 513–517 (1999).
  • Struhl G, Greenwald I. Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature398(6727), 522–525 (1999).
  • Ye Y, Lukinova N, Fortini ME. Neurogenic phenotypes and altered Notch processing in Drosophila presenilin mutants. Nature398(6727), 525–529 (1999).
  • De Strooper B, Annaert W, Cupers P et al. A presenilin-1-dependent γ-secretase-like protease mediates release of Notch intracellular domain. Nature398(6727), 518–522 (1999).
  • Lee HG, Zhu X, Castellani RJ, Nunomura A, Perry G, Smith MA. Amyloid-β in Alzheimer disease: the null versus the alternate hypotheses. J. Pharmacol. Exp. Ther.321(3), 823–829 (2007).
  • Li LM, Liu QH, Qiao JT, Zhang C. Aβ31–35-induced neuronal apoptosis is mediated by JNK-dependent extrinsic apoptosis pathway. Neurosci. Bull.25(6), 361–366 (2009).
  • Tan Z, Shi L, Schreiber SS. Differential expression of redox factor-1 associated with β-amyloid-mediated neurotoxicity. Open Neurosci. J.3, 26–34 (2009).
  • Colell A, Fernandez A, Fernandez-Checa JC. Mitochondria, cholesterol and amyloid β peptide: a dangerous trio in Alzheimer disease. J. Bioenerg. Biomembr.41(5), 417–423 (2009).
  • Shelat PB, Chalimoniuk M, Wang JH et al. Amyloid β peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J. Neurochem.106(1), 45–55 (2008).
  • Lauren J, Gimbel DA, Nygaard HB, Gilbert JW, Strittmatter SM. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature457(7233), 1128–1132 (2009).
  • Liu W, Dou F, Feng J, Yan Z. RACK1 is involved in β-amyloid impairment of muscarinic regulation of GABAergic transmission. Neurobiol. Aging DOI: 10.1016/j.neurobiolaging. 2009.10.017 (2009) (Epub ahead of print).
  • Minkeviciene R, Rheims S, Dobszay MB et al. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J. Neurosci.29(11), 3453–3462 (2009).
  • Feng Y, Yang SG, Du XT et al. Ellagic acid promotes Aβ42 fibrillization and inhibits Aβ42-induced neurotoxicity. Biochem. Biophys. Res. Commun.390(4), 1250–1254 (2009).
  • Shankar GM, Li S, Mehta TH et al. Amyloid-β protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med.14(8), 837–842 (2008).
  • De Felice FG, Velasco PT, Lambert MP et al. Aβ oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J. Biol. Chem.282(15), 11590–11601 (2007).
  • Wood JG, Mirra SS, Pollock NJ, Binder LI. Neurofibrillary tangles of Alzheimer disease share antigenic determinants with the axonal microtubule-associated protein tau (tau). Proc. Natl Acad. Sci. USA83(11), 4040–4043 (1986).
  • Zhan SS, Veerhuis R, Kamphorst W, Eikelenboom P. Distribution of β amyloid associated proteins in plaques in Alzheimer's disease and in the non-demented elderly. Neurodegeneration4(3), 291–297 (1995).
  • Allsop D, Wong CW, Ikeda S, Landon M, Kidd M, Glenner GG. Immunohistochemical evidence for the derivation of a peptide ligand from the amyloid β-protein precursor of Alzheimer disease. Proc. Natl Acad. Sci. USA85(8), 2790–2794 (1988).
  • Braak H, Braak E. Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol.1(3), 213–216 (1991).
  • Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol.82(4), 239–259 (1991).
  • Braak H, Braak E. Morphological criteria for the recognition of Alzheimer’s disease and the distribution pattern of cortical changes related to this disorder. Neurobiol. Aging15(3), 355–356; discussion 379–380 (1994).
  • Alonso AC, Grundke-Iqbal I, Iqbal K. Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat. Med.2(7), 783–787 (1996).
  • Alonso AC, Zaidi T, Grundke-Iqbal I, Iqbal K. Role of abnormally phosphorylated tau in the breakdown of microtubules in Alzheimer disease. Proc. Natl Acad. Sci. USA91(12), 5562–5566 (1994).
  • Augustinack JC, Schneider A, Mandelkow EM, Hyman BT. Specific tau phosphorylation sites correlate with severity of neuronal cytopathology in Alzheimer’s disease. Acta Neuropathol.103(1), 26–35 (2002).
  • Hyman BT, Van Hoesen GW, Wolozin BL, Davies P, Kromer LJ, Damasio AR. Alz-50 antibody recognizes Alzheimer-related neuronal changes. Ann. Neurol.23(4), 371–379 (1988).
  • Jicha GA, Bowser R, Kazam IG, Davies P. Alz-50 and MC-1, a new monoclonal antibody raised to paired helical filaments, recognize conformational epitopes on recombinant tau. J. Neurosci. Res.48(2), 128–132 (1997).
  • Fischer D, Mukrasch MD, Biernat J et al. Conformational changes specific for pseudophosphorylation at serine 262 selectively impair binding of tau to microtubules. Biochemistry48(42), 10047–10055 (2009).
  • Ding H, Matthews TA, Johnson GV. Site-specific phosphorylation and caspase cleavage differentially impact tau-microtubule interactions and tau aggregation. J. Biol. Chem.281(28), 19107–19114 (2006).
  • Zilka N, Filipcik P, Koson P et al. Truncated tau from sporadic Alzheimer’s disease suffices to drive neurofibrillary degeneration in vivo. FEBS Lett.580(15), 3582–3588 (2006).
  • Iqbal K, Novak M. From tangles to tau protein. Bratisl. Lek. Listy107(9–10), 341–342 (2006).
  • Hiraoka S, Yao TM, Minoura K et al. Conformational transition state is responsible for assembly of microtubule-binding domain of tau protein. Biochem. Biophys. Res. Commun.315(3), 659–663 (2004).
  • Guillozet-Bongaarts AL, Garcia-Sierra F, Reynolds MR et al. Tau truncation during neurofibrillary tangle evolution in Alzheimer’s disease. Neurobiol. Aging26(7), 1015–1022 (2005).
  • Mondragon-Rodriguez S, Mena R, Binder LI, Smith MA, Perry G, Garcia-Sierra F. Conformational changes and cleavage of tau in Pick bodies parallel the early processing of tau found in Alzheimer pathology. Neuropathol. Appl. Neurobiol.34(1), 62–75 (2008).
  • Luna-Munoz J, Chavez-Macias L, Garcia-Sierra F, Mena R. Earliest stages of tau conformational changes are related to the appearance of a sequence of specific phospho-dependent tau epitopes in Alzheimer’s disease. J. Alzheimers Dis.12(4), 365–375 (2007).
  • Mondragon-Rodriguez S, Basurto-Islas G, Santa-Maria I et al. Cleavage and conformational changes of tau protein follow phosphorylation during Alzheimer’s disease. Int. J. Exp. Path.89(2), 81–90 (2008).
  • Garcia-Sierra F, Mondragon-Rodriguez S, Basurto-Islas G. Truncation of tau protein and its pathological significance in Alzheimer’s disease. J. Alzheimers Dis.14(4), 401–409 (2008).
  • Markesbery WR, Carney JM. Oxidative alterations in Alzheimer’s disease. Brain Pathol.9(1), 133–146 (1999).
  • Nunomura A, Perry G, Hirai K et al. Neuronal RNA oxidation in Alzheimer’s disease and Down’s syndrome. Ann. NY Acad. Sci.89 3, 362–364 (1999).
  • Smith MA, Rudnicka-Nawrot M, Richey PL et al. Carbonyl-related posttranslational modification of neurofilament protein in the neurofibrillary pathology of Alzheimer’s disease. J. Neurochem.64(6), 2660–2666 (1995).
  • Pappolla MA, Omar RA, Kim KS, Robakis NK. Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer‘s disease. Am. J. Pathol.140(3), 621–628 (1992).
  • Nunomura A, Chiba S, Lippa CF et al. Neuronal RNA oxidation is a prominent feature of familial Alzheimer’s disease. Neurobiol. Dis.17(1), 108–113 (2004).
  • Nunomura A, Moreira PI, Takeda A, Smith MA, Perry G. Oxidative RNA damage and neurodegeneration. Curr. Med. Chem.14(28), 2968–2975 (2007).
  • Nunomura A, Perry G, Pappolla MA et al. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease. J. Neurosci.19(6), 1959–1964 (1999).
  • Strocchi P, Pession A, Dozza B. Up-regulation of cDK5/p35 by oxidative stress in human neuroblastoma IMR-32 cells. J. Cell. Biochem.88(4), 758–765 (2003).
  • Tamagno E, Robino G, Obbili A et al. H2O2 and 4-hydroxynonenal mediate amyloid β-induced neuronal apoptosis by activating JNKs and p38MAPK. Exp. Neurol.180(2), 144–155 (2003).
  • Webber KM, Smith MA, Lee HG et al. Mitogen- and stress-activated protein kinase 1: convergence of the ERK and p38 pathways in Alzheimer’s disease. J. Neurosci. Res.79(4), 554–560 (2005).
  • Munch G, Schinzel R, Loske C et al. Alzheimer’s disease – synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J. Neural Transm.105(4–5), 439–461 (1998).
  • Lu Z, Nie G, Li Y et al. Overexpression of mitochondrial ferritin sensitizes cells to oxidative stress via an iron-mediated mechanism. Antioxid. Redox Signal.11(8), 1791–1803 (2009).
  • Bowser R, Smith MA. Cell cycle proteins in Alzheimer’s disease: plenty of wheels but no cycle. J. Alzheimers Dis.4(3), 249–254 (2002).
  • Mayer C, Grummt I. Cellular stress and nucleolar function. Cell Cycle4(8), 1036–1038 (2005).
  • Tamagno E, Guglielmotto M, Aragno M et al. Oxidative stress activates a positive feedback between the g- and β-secretase cleavages of the β-amyloid precursor protein. J. Neurochem.104(3), 683–695 (2008).
  • Yan SD, Yan SF, Chen X et al. Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid β-peptide. Nat. Med.1(7), 693–699 (1995).
  • Nunomura A, Perry G, Pappolla MA et al. Neuronal oxidative stress precedes amyloid-β deposition in Down syndrome. J. Neuropathol. Exp. Neurol.59(11), 1011–1017 (2000).
  • Nunomura A, Perry G, Aliev G et al. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol.60(8), 759–767 (2001).
  • Cuajungco MP, Goldstein LE, Nunomura A et al. Evidence that the β-amyloid plaques of Alzheimer’s disease represent the redox-silencing and entombment of Aβ by zinc. J.Biol. Chem.275(26), 19439–19442 (2000).
  • Zhu X, Rottkamp CA, Boux H, Takeda A, Perry G, Smith MA. Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease. J. Neuropathol. Exp. Neurol.59(10), 880–888 (2000).
  • Zhu X, Castellani RJ, Takeda A et al. Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the ‘two hit’ hypothesis. Mech. Ageing Dev.123(1), 39–46 (2001).
  • Zhu X, Raina AK, Rottkamp CA et al. Activation and redistribution of c-jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer’s disease. J. Neurochem.76(2), 435–441 (2001).
  • Perry G, Nunomura A, Lucassen P, Lassmann H, Smith MA. Apoptosis and Alzheimer’s disease. Science282(5392), 1268–1269 (1998).
  • Mecocci P, MacGarvey U, Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann. Neurol.36(5), 747–751 (1994).
  • Holley AK, St Clair DK. Watching the watcher: regulation of p53 by mitochondria. Future Oncol.5(1), 117–130 (2009).
  • Zhu X, Raina AK, Boux H, Simmons ZL, Takeda A, Smith MA. Activation of oncogenic pathways in degenerating neurons in Alzheimer disease. Int. J. Dev. Neurosci.18(4–5), 433–437 (2000).
  • Zhu X, Raina AK, Smith MA. Cell cycle events in neurons. Proliferation or death? Am. J. Pathol.155(2), 327–329 (1999).
  • McShea A, Lee HG, Petersen RB et al. Neuronal cell cycle re-entry mediates Alzheimer disease-type changes. Biochim. Biophys. Acta1772(4), 467–472 (2007).
  • Lee HG, Casadesus G, Nunomura A et al. The neuronal expression of MYC causes a neurodegenerative phenotype in a novel transgenic mouse. Am. J. Pathol.174(3), 891–897 (2009).
  • Cuadra G, Giacobini E. Effects of cholinesterase inhibitors and clonidine coadministration on rat cortex neurotransmitters in vivo. J. Pharmacol. Exp. Ther.275(1), 228–236 (1995).
  • Pepeu G, Giovannini MG. Cholinesterase inhibitors and memory. Chem. Biol. Interact. DOI: 10.1016/j.cbi.2009.11.018 (2009) (Epub ahead of print).
  • Gandy S, Greengard P. Amyloidogenesis in Alzheimer’s disease: some possible therapeutic opportunities. Trends Pharmacol. Sci.13(3), 108–113 (1992).
  • Yamada K, Yabuki C, Seubert P et al. Aβ immunotherapy: intracerebral sequestration of Aβ by an anti-Aβ monoclonal antibody 266 with high affinity to soluble Aβ. J. Neurosci.29(36), 11393–11398 (2009).
  • Lambracht-Washington D, Qu BX, Fu M, Eagar TN, Stuve O, Rosenberg RN. DNA β-amyloid1–42 trimer immunization for Alzheimer disease in a wild-type mouse model. JAMA302(16), 1796–1802 (2009).
  • Town T. Alternative Aβ immunotherapy approaches for Alzheimer's disease. CNS Neurol. Disord. Drug Targets8(2), 114–127 (2009).
  • Santa-Maria I, Hernandez F, Del Rio J, Moreno FJ, Avila J. Tramiprosate, a drug of potential interest for the treatment of Alzheimer’s disease, promotes an abnormal aggregation of tau. Mol. Neurodegener.2, 17 (2007).
  • Middleton LE, Yaffe K. Promising strategies for the prevention of dementia. Arch. Neurol.66(10), 1210–1215 (2009).
  • Marlatt MW, Lucassen PJ, Perry G, Smith MA, Zhu X. Alzheimer’s disease: cerebrovascular dysfunction, oxidative stress, and advanced clinical therapies. J. Alzheimers Dis.15(2), 199–210 (2008).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.