115
Views
28
CrossRef citations to date
0
Altmetric
Review

Can peripheral leukocytes be used as Alzheimer’s disease biomarkers?

, , &
Pages 1623-1633 | Published online: 09 Jan 2014

References

  • Selkoe DJ. Alzheimer’s disease: genes, proteins, and therapy. Physiol. Rev.81(2), 741–766 (2001).
  • Hebert LE, Scherr PA, Bienias JL, Bennett DA, Evans DA. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch. Neurol.60(8), 1119–1122 (2003).
  • Plassman BL, Langa KM, Fisher GG et al. Prevalence of dementia in the United States: the Aging, Demographics, and Memory study. Neuroepidemiology29(1–2), 125–132 (2007).
  • Brookmeyer R, Gray S, Kawas C. Projections of Alzheimers-disease in the United States and the public health impact of delaying disease onset. Am. J. Public Health88(9), 1337–1342 (1998).
  • Petersen RC. Challenges of epidemiological studies of mild cognitive impairment. Alzheimer Dis. Assoc. Disord.18(1), 1–2 (2004).
  • Tanzi RE. Alzheimer’s disease and related dementias: the road to intervention. Exp. Gerontol.35(4), 433–437 (2000).
  • Hardy J, Allsop D. Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol. Sci.12(10), 383–388 (1991).
  • Sipe JD, Cohen AS. Review: history of the amyloid fibril. J. Struct. Biol.130(2–3), 88–98 (2000).
  • Walsh DM, Klyubin I, Fadeeva JV, Rowan MJ, Selkoe DJ. Amyloid-β oligomers: their production, toxicity and therapeutic inhibition. Biochem. Soc. Trans.30(4), 552–557 (2002).
  • Benzing WC, Wujek JR, Ward EK et al. Evidence for glial-mediated inflammation in aged APP(SW) transgenic mice. Neurobiol. Aging20(6), 581–589 (1999).
  • McGowan E, Sanders S, Iwatsubo T et al. Amyloid phenotype characterization of transgenic mice overexpressing both mutant amyloid precursor protein and mutant presenilin 1 transgenes. Neurobiol. Dis.6(4), 231–244 (1999).
  • McGeer EG, McGeer PL. The importance of inflammatory mechanisms in Alzheimer disease. Exp. Gerontol.33(5), 371–378 (1998).
  • McGeer EG, McGeer PL. Inflammatory processes in Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry27(5), 741–749 (2003).
  • Akiyama H, Barger S, Barnum S et al. Inflammation and Alzheimer’s disease. Neurobiol. Aging21(3), 383–421 (2000).
  • Tan J, Town T, Paris D et al. Microglial activation resulting from CD40–CD40L interaction after β-amyloid stimulation. Science286(5448), 2352–2355 (1999).
  • Tan J, Town T, Mullan M. CD40–CD40L interaction in Alzheimer’s disease. Curr. Opin. Pharmacol.2(4), 445–451 (2002).
  • Tan J, Town T, Crawford F et al. Role of CD40 ligand in amyloidosis in transgenic Alzheimer’s mice. Nat. Neurosci.5(12), 1288–1293 (2002).
  • Town T, Tan J, Mullan M. CD40 signaling and Alzheimer’s disease pathogenesis. Neurochem. Int.39(5–6), 371–380 (2001).
  • Town T, Nikolic V, Tan J. The microglial ‘activation’ continuum: from innate to adaptive responses. J. Neuroinflammation2, 24 (2005).
  • Wyss-Coray T, Mucke L. Inflammation in neurodegenerative disease a double-edged sword. Neuron35(3), 419–432 (2002).
  • in t’ Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N. Engl. J. Med.345(21), 1515–1521 (2001).
  • Szekely CA, Thorne JE, Zandi PP et al. Nonsteroidal anti-inflammatory drugs for the prevention of Alzheimer’s disease: a systematic review. Neuroepidemiology23(4), 159–169 (2004).
  • Szekely CA, Town T, Zandi PP. NSAIDs for the chemoprevention of Alzheimer’s disease. Subcell. Biochem.42, 229–248 (2007).
  • McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology47(2), 425–432 (1996).
  • Zandi PP, Anthony JC, Hayden KM, Mehta K, Mayer L, Breitner JC. Reduced incidence of AD with NSAID but not H2 receptor antagonists: the Cache County study. Neurology59(6), 880–886 (2002).
  • Stewart WF, Kawas C, Corrada M, Metter EJ. Risk of Alzheimer’s disease and duration of NSAID use. Neurology48(3), 626–632 (1997).
  • Cornelius C, Fastbom J, Winblad B, Viitanen M. Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology23(3), 135–143 (2004).
  • Szekely CA, Breitner JC, Fitzpatrick AL et al. NSAID use and dementia risk in the Cardiovascular Health study: role of APOE and NSAID type. Neurology70(1), 17–24 (2008).
  • Breitner JC, Haneuse SJ, Walker R et al. Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort. Neurology72(22), 1899–1905 (2009).
  • Arvanitakis Z, Grodstein F, Bienias JL et al. Relation of NSAIDs to incident AD, change in cognitive function, and AD pathology. Neurology70(23), 2219–2225 (2008).
  • Reines SA, Block GA, Morris JC et al. Rofecoxib: no effect on Alzheimer’s disease in a 1-year, randomized, blinded, controlled study. Neurology62(1), 66–71 (2004).
  • Rogers J, Kirby LC, Hempelman SR et al. Clinical trial of indomethacin in Alzheimer’s disease. Neurology43(8), 1609–1611 (1993).
  • Scharf S, Mander A, Ugoni A, Vajda F, Christophidis N. A double-blind, placebo-controlled trial of diclofenac/misoprostol in Alzheimer’s disease. Neurology53(1), 197–201 (1999).
  • Aisen PS, Schmeidler J, Pasinetti GM. Randomized pilot study of nimesulide treatment in Alzheimer’s disease. Neurology58(7), 1050–1054 (2002).
  • Aisen PS, Schafer KA, Grundman M et al. Effects of rofecoxib or naproxen vs placebo on Alzheimer disease progression: a randomized controlled trial. JAMA289(21), 2819–2826 (2003).
  • Thal LJ, Ferris SH, Kirby L et al. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology30(6), 1204–1215 (2005).
  • ADAPT Research Group, Lyketsos CG, Breitner JC et al. Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial. Neurology68(21), 1800–1808 (2007).
  • Franceschi C, Capri M, Monti D et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev.128(1), 92–105 (2007).
  • Giunta B, Fernandez F, Nikolic WV et al. Inflammaging as a prodrome to Alzheimer’s disease. J. Neuroinflammation5, 51 (2008).
  • Town T, Tan J, Flavell RA, Mullan M. T-cells in Alzheimer’s disease. Neuromolecular Med.7(3), 255–264 (2005).
  • Flurkey K, Stadecker M, Miller RA. Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency. Eur. J. Immunol.22(4), 931–935 (1992).
  • Monsonego A, Zota V, Karni A et al. Increased T cell reactivity to amyloid β protein in older humans and patients with Alzheimer disease. J. Clin. Invest.112(3), 415–422 (2003).
  • Dutton RW, Bradley LM, Swain SL. T cell memory. Annu. Rev. Immunol.16, 201–223 (1998).
  • Tan J, Town T, Abdullah L et al. CD45 isoform alteration in CD4+ T cells as a potential diagnostic marker of Alzheimer’s disease. J. Neuroimmunol.132(1–2), 164–172 (2002).
  • Burke JR, Roses AD. Genetics of Alzheimer’s disease. Int. J. Neurol.25–26, 41–51 (1991).
  • Mayeux R, Stern Y, Ottman R et al. The apolipoprotein epsilon 4 allele in patients with Alzheimer’s disease. Ann. Neurol.34(5), 752–754 (1993).
  • Roses AD. Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer’s disease. Ann. Neurol.38(1), 6–14 (1995).
  • Roses AD. Genetic testing and Alzheimer disease: the promise. Alzheimer Dis. Assoc. Disord.12(Suppl. 3), S3–S9 (1998).
  • Larbi A, Pawelec G, Witkowski JM et al. Dramatic shifts in circulating CD4 but not CD8 T cell subsets in mild Alzheimer’s disease. J. Alzheimers Dis.17(1), 91–103 (2009).
  • Jago CB, Yates J, Camara NO, Lechler RI, Lombardi G. Differential expression of CTLA-4 among T cell subsets. Clin. Exp. Immunol.136(3), 463–471 (2004).
  • Itagaki S, McGeer PL, Akiyama H. Presence of T-cytotoxic suppressor and leucocyte common antigen positive cells in Alzheimer’s disease brain tissue. Neurosci. Lett.91(3), 259–264 (1988).
  • Rogers J, Luber-Narod J, Styren SD, Civin WH. Expression of immune system-associated antigens by cells of the human central nervous system: relationship to the pathology of Alzheimer’s disease. Neurobiol. Aging9(4), 339–349 (1988).
  • Togo T, Akiyama H, Iseki E et al. Occurrence of T cells in the brain of Alzheimer’s disease and other neurological diseases. J. Neuroimmunol.124(1–2), 83–92 (2002).
  • Pirttila T, Mattinen S, Frey H. The decrease of CD8-positive lymphocytes in Alzheimer’s disease. J. Neurol. Sci.107(2), 160–165 (1992).
  • Skias D, Bania M, Reder AT, Luchins D, Antel JP. Senile dementia of Alzheimer’s type (SDAT): reduced T8+-cell-mediated suppressor activity. Neurology35(11), 1635–1638 (1985).
  • Shalit F, Sredni B, Brodie C, Kott E, Huberman M. T lymphocyte subpopulations and activation markers correlate with severity of Alzheimer’s disease. Clin. Immunol. Immunopathol.75(3), 246–250 (1995).
  • Bonotis K, Krikki E, Holeva V, Aggouridaki C, Costa V, Baloyannis S. Systemic immune aberrations in Alzheimer’s disease patients. J. Neuroimmunol.193(1–2), 183–187 (2008).
  • Leffell MS, Lumsden L, Steiger WA. An analysis of T lymphocyte subpopulations in patients with Alzheimer’s disease. J. Am. Geriatr. Soc.33(1), 4–8 (1985).
  • Singh VK. Neuroimmune axis as a basis of therapy in Alzheimer’s disease. Prog. Drug Res.34, 383–393 (1990).
  • Ikeda T, Yamamoto K, Takahashi K, Yamada M. Immune system-associated antigens on the surface of peripheral blood lymphocytes in patients with Alzheimer’s disease. Acta Psychiatr. Scand.83(6), 444–448 (1991).
  • Richartz-Salzburger E, Batra A, Stransky E et al. Altered lymphocyte distribution in Alzheimer’s disease. J. Psychiatr. Res.41(1–2), 174–178 (2007).
  • Hu GR, Walls RS, Creasey H, McCusker E, Broe GA. Peripheral blood lymphocyte subset distribution and function in patients with Alzheimer’s disease and other dementias. Aust. NZ J. Med.25(3), 212–217 (1995).
  • Chen K, Huang J, Gong W, Zhang L, Yu P, Wang JM. CD40/CD40L dyad in the inflammatory and immune responses in the central nervous system. Cell. Mol. Immunol.3(3), 163–169 (2006).
  • Abdel-Haq N, Hao HN, Lyman WD. Cytokine regulation of CD40 expression in fetal human astrocyte cultures. J. Neuroimmunol.101(1), 7–14 (1999).
  • Tan J, Town T, Mori T et al. CD40 is expressed and functional on neuronal cells. EMBO J.21(4), 643–652 (2002).
  • Togo T, Akiyama H, Kondo H et al. Expression of CD40 in the brain of Alzheimer’s disease and other neurological diseases. Brain Res.885(1), 117–121 (2000).
  • Townsend KP, Town T, Mori T et al. CD40 signaling regulates innate and adaptive activation of microglia in response to amyloid β-peptide. Eur. J. Immunol.35(3), 901–910 (2005).
  • Tan J, Town T, Suo Z et al. Induction of CD40 on human endothelial cells by Alzheimer’s β-amyloid peptides. Brain Res. Bull.50(2), 143–148 (1999).
  • Tan J, Town T, Paris D et al. Activation of microglial cells by the CD40 pathway: relevance to multiple sclerosis. J. Neuroimmunol.97(1–2), 77–85 (1999).
  • Aloisi F, Ria F, Penna G, Adorini L. Microglia are more efficient than astrocytes in antigen processing and in Th1 but not Th2 cell activation. J. Immunol.160(10), 4671–4680 (1998).
  • Calingasan NY, Erdely HA, Altar CA. Identification of CD40 ligand in Alzheimer’s disease and in animal models of Alzheimer’s disease and brain injury. Neurobiol. Aging23(1), 31–39 (2002).
  • van Kooten C, Banchereau J. CD40–CD40 ligand. J. Leukoc. Biol.67(1), 2–17 (2000).
  • Grewal IS, Flavell RA. CD40 and CD154 in cell-mediated immunity. Annu. Rev. Immunol.16, 111–135 (1998).
  • Grewal IS, Foellmer HG, Grewal KD et al. Requirement for CD40 ligand in costimulation induction, T cell activation, and experimental allergic encephalomyelitis. Science273(5283), 1864–1867 (1996).
  • Obradovic SD, Antovic JP, Antonijevic NM et al. Elevations in soluble CD40 ligand in patients with high platelet aggregability undergoing percutaneous coronary intervention. Blood Coagul. Fibrinolysis20(4), 283–289 (2009).
  • Lessiani G, Dragani A, Falco A, Fioritoni F, Santilli F, Davi G. Soluble CD40 ligand and endothelial dysfunction in aspirin-treated polycythaemia vera patients. Br. J. Haematol.145(4), 538–540 (2009).
  • Mocali A, Cedrola S, Della Malva N et al. Increased plasma levels of soluble CD40, together with the decrease of TGF β 1, as possible differential markers of Alzheimer disease. Exp. Gerontol.39(10), 1555–1561 (2004).
  • Holcomb L, Gordon MN, McGowan E et al. Accelerated alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat. Med.4(1), 97–100 (1998).
  • Todd Roach J, Volmar CH, Dwivedi S et al. Behavioral effects of CD40–CD40L pathway disruption in aged PSAPP mice. Brain Res.1015(1–2), 161–168 (2004).
  • Desideri G, Cipollone F, Necozione S et al. Enhanced soluble CD40 ligand and Alzheimer’s disease: evidence of a possible pathogenetic role. Neurobiol. Aging29(3), 348–356 (2008).
  • Giunta B, Figueroa KP, Town T, Tan J. Soluble CD40 ligand in dementia. Drugs Future34(4), 333–339 (2009).
  • Harman D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol.11(3), 298–300 (1956).
  • Harman D. Origin and evolution of the free radical theory of aging: a brief personal history, 1954–2009. Biogerontology (2009).
  • Smith MA, Kutty RK, Richey PL et al. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer’s disease. Am. J. Pathol.145(1), 42–47 (1994).
  • Smith MA, Tabaton M, Perry G. Early contribution of oxidative glycation in Alzheimer disease. Neurosci. Lett.217(2–3), 210–211 (1996).
  • Eckert A, Cotman CW, Zerfass R, Hennerici M, Muller WE. Lymphocytes as cell model to study apoptosis in Alzheimer’s disease: vulnerability to programmed cell death appears to be altered. J. Neural. Transm. Suppl.54, 259–267 (1998).
  • Schindowski K, Leutner S, Muller WE, Eckert A. Age-related changes of apoptotic cell death in human lymphocytes. Neurobiol. Aging21(5), 661–670 (2000).
  • Eckert A, Schindowski K, Leutner S et al. Alzheimer’s disease-like alterations in peripheral cells from presenilin-1 transgenic mice. Neurobiol. Dis.8(2), 331–342 (2001).
  • Sulger J, Dumais-Huber C, Zerfass R, Henn FA, Aldenhoff JB. The calcium response of human T lymphocytes is decreased in aging but increased in Alzheimer’s dementia. Biol. Psychiatry45(6), 737–742 (1999).
  • Richartz E, Noda S, Schott K, Gunthner A, Lewczuk P, Bartels M. Increased serum levels of CD95 in Alzheimer’s disease. Dement. Geriatr. Cogn. Disord.13(3), 178–182 (2002).
  • Lombardi VR, Garcia M, Rey L, Cacabelos R. Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer’s disease (AD) individuals. J. Neuroimmunol.97(1–2), 163–171 (1999).
  • Tavolato B, Argentiero V. Immunological indices in presenile Alzheimer’s disease. J. Neurol. Sci.46(3), 325–331 (1980).
  • Tollefson GD, Godes M, Warren JB, Haus E, Luxenberg M, Garvey M. Lymphopenia in primary degenerative dementia. J. Psychiatr. Res.23(3–4), 191–199 (1989).
  • Dysken MW, Minichiello MD, Hill JL et al. Distribution of peripheral lymphocytes in Alzheimer patients and controls. J. Psychiatr. Res.26(3), 213–218 (1992).
  • Magaki S, Yellon SM, Mueller C, Kirsch WM. Immunophenotypes in the circulation of patients with mild cognitive impairment. J. Psychiatr. Res.42(3), 240–246 (2008).
  • Bullido MJ, Munoz-Fernandez MA, Recuero M, Fresno M, Valdivieso F. Alzheimer’s amyloid precursor protein is expressed on the surface of hematopoietic cells upon activation. Biochim. Biophys. Acta1313(1), 54–62 (1996).
  • Pallister C, Jung SS, Shaw I, Nalbantoglu J, Gauthier S, Cashman NR. Lymphocyte content of amyloid precursor protein is increased in Down’s syndrome and aging. Neurobiol. Aging18(1), 97–103 (1997).
  • Jung SS, Gauthier S, Cashman NR. β-amyloid precursor protein is detectable on monocytes and is increased in Alzheimer’s disease. Neurobiol. Aging20(3), 249–257 (1999).
  • Stieler JT, Lederer C, Bruckner MK et al. Impairment of mitogenic activation of peripheral blood lymphocytes in Alzheimer’s disease. Neuroreport12(18), 3969–3972 (2001).
  • Lopez OL, Rabin BS, Huff FJ. Serum auto-antibodies in Alzheimer’s disease. Acta Neurol. Scand.84(5), 441–444 (1991).
  • Du Y, Dodel R, Hampel H et al. Reduced levels of amyloid β-peptide antibody in Alzheimer disease. Neurology57(5), 801–805 (2001).
  • Hyman BT, Smith C, Buldyrev I et al. Autoantibodies to amyloid-β and Alzheimer’s disease. Ann. Neurol.49(6), 808–810 (2001).
  • Weksler ME, Relkin N, Turkenich R, LaRusse S, Zhou L, Szabo P. Patients with Alzheimer disease have lower levels of serum anti-amyloid peptide antibodies than healthy elderly individuals. Exp. Gerontol.37(7), 943–948 (2002).
  • Brettschneider S, Morgenthaler NG, Teipel SJ et al. Decreased serum amyloid β(1–42) autoantibody levels in Alzheimer’s disease, determined by a newly developed immuno-precipitation assay with radiolabeled amyloid β(1–42) peptide. Biol. Psychiatry57(7), 813–816 (2005).
  • Baril L, Nicolas L, Croisile B et al. Immune response to Aβ-peptides in peripheral blood from patients with Alzheimer’s disease and control subjects. Neurosci. Lett.355(3), 226–230 (2004).
  • Nath A, Hall E, Tuzova M et al. Autoantibodies to amyloid β-peptide (Aβ) are increased in Alzheimer’s disease patients and Aβ antibodies can enhance Aβ neurotoxicity: implications for disease pathogenesis and vaccine development. Neuromolecular Med.3(1), 29–39 (2003).
  • Gruden MA, Davudova TB, Malisauskas M et al. Autoimmune responses to amyloid structures of Aβ(25–35) peptide and human lysozyme in the serum of patients with progressive Alzheimer’s disease. Dement. Geriatr. Cogn. Disord.18(2), 165–171 (2004).
  • Mruthinti S, Buccafusco JJ, Hill WD et al. Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Aβ and RAGE peptides. Neurobiol. Aging25(8), 1023–1032 (2004).
  • Wilson JS, Mruthinti S, Buccafusco JJ et al. Anti-RAGE and Aβ immunoglobulin levels are related to dementia level and cognitive performance. J. Gerontol. A. Biol. Sci. Med. Sci.64(2), 264–271 (2009).
  • Myagkova MA, Gavrilova SI, Lermontova NN et al. Content of autoantibodies to bradykinin and β-amyloid(1–42) as a criterion for biochemical differences between Alzheimer’s dementias. Bull. Exp. Biol. Med.136(1), 49–52 (2003).
  • Britschgi M, Olin CE, Johns HT et al. Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer’s disease. Proc. Natl Acad. Sci. USA106(29), 12145–12150 (2009).
  • Moir RD, Tseitlin KA, Soscia S, Hyman BT, Irizarry MC, Tanzi RE. Autoantibodies to redox-modified oligomeric Aβ are attenuated in the plasma of Alzheimer’s disease patients. J. Biol. Chem.280(17), 17458–17463 (2005).
  • Sun JC, Lanier LL. Natural killer cells remember: an evolutionary bridge between innate and adaptive immunity? Eur. J. Immunol.39(8), 2059–2064 (2009).
  • Araga S, Kagimoto H, Funamoto K, Takahashi K. Reduced natural killer cell activity in patients with dementia of the Alzheimer type. Acta Neurol. Scand.84(3), 259–263 (1991).
  • Solerte SB, Fioravanti M, Severgnini S et al. Enhanced cytotoxic response of natural killer cells to interleukin-2 in Alzheimer’s disease. Dementia7(6), 343–348 (1996).
  • Masera RG, Prolo P, Sartori ML et al. Mental deterioration correlates with response of natural killer (NK) cell activity to physiological modifiers in patients with short history of Alzheimer’s disease. Psychoneuroendocrinology27(4), 447–461 (2002).
  • Prolo P, Chiappelli F, Angeli A et al. Physiologic modulation of natural killer cell activity as an index of Alzheimer’s disease progression. Bioinformation1(9), 363–366 (2007).
  • Leblhuber F, Walli J, Demel U, Tilz GP, Widner B, Fuchs D. Increased serum neopterin concentrations in patients with Alzheimer’s disease. Clin. Chem. Lab. Med.37(4), 429–431 (1999).
  • Murr C, Fuith LC, Widner B, Wirleitner B, Baier-Bitterlich G, Fuchs D. Increased neopterin concentrations in patients with cancer: indicator of oxidative stress? Anticancer Res.19(3A), 1721–1728 (1999).
  • Hull M, Pasinetti GM, Aisen PS. Elevated plasma neopterin levels in Alzheimer disease. Alzheimer Dis. Assoc. Disord.14(4), 228–230 (2000).
  • Zhang L, Fiala M, Cashman J et al. Curcuminoids enhance amyloid-β uptake by macrophages of Alzheimer’s disease patients. J. Alzheimers Dis.10(1), 1–7 (2006).
  • Town T, Laouar Y, Pittenger C et al. Blocking TGF-β-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat. Med.14(6), 681–687 (2008).
  • Town T. Alternative Aβ immunotherapy approaches for Alzheimer’s disease. CNS Neurol. Disord. Drug Targets8(2), 114–127 (2009).
  • Rezai-Zadeh K, Gate D, Town T. CNS infiltration of peripheral macrophages: D-day for neurodegenerative disease? J. Neuroimmune Pharmacol. (2009) (In press).
  • Avagyan H, Goldenson B, Tse E et al. Immune blood biomarkers of Alzheimer disease patients. J. Neuroimmunol.210(1–2), 67–72 (2009).
  • Fiala M, Liu PT, Espinosa-Jeffrey A et al. Innate immunity and transcription of MGAT-III and Toll-like receptors in Alzheimer’s disease patients are improved by bisdemethoxycurcumin. Proc. Natl Acad. Sci. USA104(31), 12849–12854 (2007).
  • Kusdra L, Rempel H, Yaffe K, Pulliam L. Elevation of CD69+ monocyte/macrophages in patients with Alzheimer’s disease. Immunobiology202(1), 26–33 (2000).
  • Song C, Vandewoude M, Stevens W et al. Alterations in immune functions during normal aging and Alzheimer’s disease. Psychiatry Res.85(1), 71–80 (1999).
  • Licastro F, Morini MC, Davis LJ et al. Increased chemiluminescence response of neutrophils from the peripheral blood of patients with senile dementia of the Alzheimer’s type. J. Neuroimmunol.51(1), 21–26 (1994).
  • Scali C, Prosperi C, Bracco L et al. Neutrophils CD11b and fibroblasts PGE(2) are elevated in Alzheimer’s disease. Neurobiol. Aging23(4), 523–530 (2002).
  • Koltringer P, Reiseeker F, Eber O, Langsteger W, Lind P. The rheology of erythrocytes and granulocytes in Alzheimer’s disease and multi-infarction-dementia: a prospective study. J. Neural. Trasm.1, 91 (1989).
  • Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin. Pharmacol. Ther.69(3), 89–95 (2001).
  • Ray S, Britschgi M, Herbert C et al. Classification and prediction of clinical Alzheimer’s diagnosis based on plasma signaling proteins. Nat. Med.13(11), 1359–1362 (2007).
  • Frank R, Hargreaves R. Clinical biomarkers in drug discovery and development. Nat. Rev. Drug Discov.2(7), 566–580 (2003).

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:

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:

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.