While the etiopathogenesis of Alzheimer’s disease (AD) still remains unresolved, a growing body of evidence indicates the involvement of the immune system. Yet, both character and the significance of the observed alterations are matter of dispute.
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References
Aisen PS, Davies KL (1994) Inflammatory mechanisms in Alzheimer’s disease. Implications for therapy. Am J Psychiatry 51:1105–1113
Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM et al (2000) Inflammation and Alzheimer’s disease. Neurobiol Aging 21:383–421
Androsova LV, Sekirina TP, Selezneva ND, Koliaskin G, Gavrilova SI (1995) Changes in the immunological parameters in Alzheimer’s disease. Their relation to disease severity. Zhurnal nevropatologii I psikhiatrii imeni SS Korsakova Moscow 95:24–27
Apelt J, Schliebs R (2001) ß-amyloid-induced glial expression of both pro and antiinflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res 894:21–30
Bagli M, Papassotiropoulos A, Hampel H, Becker K, Jessen F, Bürger K, Ptok U, Rao ML, Möller HJ, Heun R (2003) Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer’s disease. Eur Arch Psychiatry Clin Neurosci 253:44–48
Beharka AA, Meydani M, Wu D, Leka LS, Meydani A, Meydani SN (2001) Interleukin–6 production does not increase with age. J Gerontol A Biol Sci Med Sci 56:81–88
Blasko I, Grubeck-Loebenstein B (2003) Role of the immune system in the pathogenesis, prevention and treatment of Alzheimer’s disease. Drugs Aging 20:101–113
Blum-Degen D, Müller T, Kuhn W, Gerlach M, Przuntek H, Riederer P (1995) Interleukin-1ß and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer’s and de novo Parkinsons’s disease patients. Neurosci Lett 292:17–20
Cacabelos R, Alvarez XA, Franco-Maside A, Fernández-Novoa L, Caamaño J (1994) Serum tumor necrosis factor (TNF) in Alzheimer’s disease and multiinfarct-dementia. Methods Find Exp Clin Pharmacol 16:29–35
Cirrito JR, Holtzman DM (2003) Amyloid beta and Alzheimer’s disease therapeutics: the devil may be in the details. J Clin Invest 112:321–323
De la Monte SM, Luong T, Neely TR, Robinson D, Wands JR (2000) Mitochondrial DNA damage as a mechanism of cell loss in Alzheimer disease. Lab Invest 80:1323–1335
De Luigi A, Fragiacomo C, Lucca U, Quadri P, Tattamanti M, De Simoni MG (2001) Inflammatory markers in Alzheimer’s disease and multi-infarct dementia. Mech Ageing Dev 122:1985–1995
De Witt DA, Perry G, Cohen M, Doller C, Siver J (1998) Astrocytes regulate microglial phagocytosis of senile plaque cores of Alzheimer’s disease. Exp Neurol 149:329–340
DiCarlo G, Wilcock D, Henderson D, Gordon M, Morgan D (2001) Intrahippocampal LPS injections reduce A beta load in APP and PS1 transgenic mice. Neurobiol Aging 22:1007–1012
Dickson DW, Sunhee CL, Brosnan CF, Sinicropi S, Vlassara H, Yen SC (1996) Neuroimmunology of aging and Alzheimer’s disease with emphasis on cytokines. In:Ransohoff RM, Benveniste EN (eds) Cytokines and the CNS. Boca Raton, CRC Press, pp 239–267
Du Y, Dodel R, Hampel H (2001) Reduced levels of amyloid beta-peptide antibody in Alzheimer’s disease. Neurology 57:801–805
Effros RB (1998) Replicative senescence in the immune system: Impact of the Hayflick limit on T cell function in the elderly. Am J Hum Genet 62:1003–1007
Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci U S A 94:4080–4085
Esumi E, Araga S, Takahashi K (1991) Serum interleukin-2 levels in patients with dementia of the Alzheimer type. Acta Neurol Scand 84:65–67
Fiala M, Liu, Sayre J, Pop V, Brahmandam V, Graves MC, Vinters HV (2002) Cyclooxidase-2-positive macrophages infiltrate the Alzheimer’s disease brain and damage the blood-brain barrier. Eur J Clin Invest 32:360–371
Fujiwara Y (1996) The mechanisms of aging and perspective for elimination of deleterious effects. Nippon Ronen Igakkai Zhassi 33:499–502
Gasiorowski K, Leszek J (1997) A proposed new strategy of immunotherapy for Alzheimer’s disease. Med Hypotheses 49:319–326
Gillis S, Kozak R, Durante M, Weksler ME (1981) Immunological studies of aging. Decreased product of and response to T cell growth factor by lymphocytes from aged humans. J Clin Invest 67:937–942
Giubilei F, Antonini G, Montesperelli C, Sepe-Monti M, Cannoni S, Pichi A et al (2003) T cell response to amyloid-beta and to mitochondrial antigens in Alzheimer’s disease. Dement Geriatr Cogn Disord 16:35–38
Grossmann A, Kukull WA, Jinneman JC, Bird TD, Villacres EC, Larson EB et al (1993) Intracellular calcium response is reduced in CD4+lymphocytes in Alzheimer’s disease and in older persons with Down’s syndrome. Neurobiol Aging 14:177–185
Hartmann A, Veldhuis JD, Deuschle M, Standhardt H, Heuser I (1997) Twentyfour hour cortisol release profiles in patients with Alzheimer’s and Parkinson’s Disease compared to normal controls: ultradian secretory pulsatility and diurnal variation. Neurobiol Aging 18:285–289
Huberman M, Shalit F, Roth-Deri I, Gutman B, Brodie C, Kott E et al (1994) Correlation of cytokine secretion by mononuclear cells of Alzheimer patients and their disease stage. J Neuroimmunol 52:147–152
Hüll M, Strauss S, Berger M, Volk B, Bauer J (1996) Inflammatory mechanisms in Alzheimeŕs Disease. Eur Arch Psychiatry Clin Neurosci 246:124–128
Joseph J, Shukitt-Hale B, Denisova NA, Martin A, Gerry G, Smith MA (2001) Copernicus revisited: Amyloid beta in Alzheimer’s disease. Neurobiol Aging 22:131–146
Kalman J, Juhasz A, Laird G, Dickens P, Jardanhazy T, Rimanoczy A et al (1997) Serum Il-6 levels correlate with the severity of dementia in Down syndrome and in Alzheimer’s disease. Acta Neurol Scand 96:236–240
Lanzrein AD, Johnston PM, Perry VH, Jobst KA, King EM, Smith D (1998) Longitudinal study of inflammatory factors in serum, cerebrospinal fluid, and brain tissue in Alzheimer’s disease: Interleukin -1b, Interleukin-6, Interleukin-1 receptor antagonist, tumor necrosis factor-α, the soluble tumor necrosis factor receptors I and II, and α1-antichymotrypsin. Alzheimer Dis Ass Disord 12:215–227
Lemere CA, Spooner ET, LaFrancois J et al (2003) Evidence for peripheral clearance of cerebral Abeta protein following chronic, active Abeta immunization in PSAPP mice. Neurobiol Dis 14: 10–18
Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C et al (2000) Increased plasma levels of interleukin-1, interleukin-6, and alpha-1-antichymotrypsin in patients with Alzheimer’s disease: peripheral inflammation or signals form the brain? J Neuroimmunol 103:97–102
Linke RP (1996) Amyloidosen. In: Peter HH, Pichler WJ (eds) Klinische Immunologie. Urban&Schwarzenberg, Munich, Vienna, Baltimore, pp 822–833
Lloberas J, Celada A (2002) Effect of aging on macrophage function. Exp Gerontol 37:1325–1331
Lombardi VR, Garcia M, Rey R, Cacabelos R (1999) Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer’s Disease (AD) individuals. J Neuroimmunol 97:163–171
Lue LF, Walker DG (2002) Modeling Alzheimer’s disease immune therapy mechanisms: interactions of human postmortem microglia with antibody-opsonized amyloid-beta peptide. J Neurosci Res 70:599–610
März P, Heese K, Hock C, Golombowski S, Müller-Spahn F, Rose-John S et al (1997) Interleukin-6 (IL-6) and soluble forms of IL-6 receptors are not altered in cerebrospinal fluid of Alzheimer’s disease patients. Neurosci Lett 239:29–32
McGeer PL, McGeer EG (1999) Inflammation of the brain in Alzheimer’s disease: implications for therapy. J Leukoc Biol 65:409–415
McGeer EG, McGeer PL (2003) Inflammatory processes in Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 27:741–749
McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimeŕs Disease: Report of the NINCDS-ADRDA Work Group under auspices of Department of Health and Human Services Task Force on Alzheimeŕs Disease. Neurology 34:939–944
Mecocci P, Polidori M-C, Ingegni T, Cherubini A, Chionne F, Cecchetti R et al (1998) Oxidative damage to DNA in lymphocytes from AD patients. Neurology 51:1014–1017
Mrak RE, Sheng JGW, Griffin ST (1995) Glial cytokines in Alzheimer’s disease. Review and pathogenetic implications. Hum Pathol 26:816–823
Paganelli R, Di Iorio A, Patricelli L, Ripani F, Sparvieri E, Faricelli R et al (2002) Proinflammatory cytokines in sera of elderly patients with dementia: levels in vascular injury are higher than those of mild-moderate Alzheimer’s disease patients. Exp Gerontol 37:257–263
Panossian LA, Porter VR, Valenzuela HF, Zhu X, Reback E, Materman D et al (2003) Telomere shortening in T cells correlates with Alzheimer disease status. Neurobiol Aging 24:77–84
Park E, Alberti J, Mehta P, Dalton A, Sersen E, Schuller-Levis G (2000) Partial impairment of immune functions in peripheral blood leukocytes from aged men with Down’s Syndrome. Clin Immunol 95:62
Popovic M, Caballero-Bleda M, Puelles L, Popvoc N (1998) Importance of immunological and inflammatory processes in the pathogenesis and therapy of Alzheimer’s disease. Int J Neurosci 95:203–236
Reale M, Iarlori C, Gambi F, Feliciani C, Salone A, Ronma L et al (2004) Treatment with acetylcholinesterase inhibitor in Alzheimer patients modulates the expression and production of the pro-inflammatory and anti-inflammatory cytokines. J Neuroimmunol 148:162–171
Richartz E, Klein R, Stransky E et al (2004) Autoantibody reactivity in serum and cerebrospinal fluid of patients with Alzheimer’s disease. Neurol Psychiatr Bain Res 11:145–148
Richartz E, Batra A, Stransky E, Wormstall H, Lewzcuk P, Bartels M, Schott KW (2005) Decline of immune responsiveness: a pathogenetic factor in Alzheimer’s disease? J Psychiat Res 39:535–543
Rogers J, Strohmeyer R, Kovolowski CJ, Li R (2002) Microglia and inflammatory mechanisms in the clearance of amyloid ß peptide. Glia 40:260–269
Sala G, Galimberti G, Canevari C, Raggi MA, Isella V, Facheris M et al (2004) Peripheral cytokine release in Alzheimer patients: correlation with disease severity. Neurobiol Aging 24:909–914
Sasaki A, Yamaguchi H, Ogawa A, Sugihara S, Nagazato Y (1997) Microglial activation in early stages of amyloid beta protein deposition. Acta Neuropathol (Berlin) 94:316–322
Schott K, Wormstall H, Dietrich M, Klein R, Batra A (1996) Autoantibody reactivity in serum of patients with Alzheimer’s disease and other age-related dementias. Psychiatry Res 59:251–254
Schott K, Batra A, Richartz W, Sarkar R, Bartels M, Buchkremer G (1997) Serumantibodies to brain lipids in mental disorders. Neurol Psychiatry Brain Res 5:31–34
Schenk D, Barbour R, Dunn W, Gordon G, Grajeda H, Guido T et al (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177
Sengun IS, Appel SH (2003) Serum anti-Fas antibody levels in amyotrophic lateral sclerosis. J Neuroimmunol 142(1–2):137–140
Singh VK (1994) Studies of neuroimmune markers in Alzheimer’s disease. Mol Neurobiol 9:73–81
Singh VK, Guthikonda P (1997) Circulating cytokines in Alzheimer’s disease. J Psychiatr Res 31:657–660
Streit WJ (2001) Microglia and macrophages in the developing CNS. Neurotoxicology 22:619–624
Streit WJ (2002) Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 40:133–139
Sulger J, Dumais Huber C, Zerfass R, Henn FA, Aldenhoff JB (1999) The calcium response of human T lymphocytes is decreased in aging but increased in Alzheimer dementia. Biol Psychiatry 45:737–742
Tarkowksi E, Blennow K, Wallin A, Tarkowksi A (1999) Intracerebral production of tumor necrosis factor-?, a local neuroprotective agent in Alzheimer’s disease and vascular dementia. J Clin Immunol 19:223–230
Trieb K, Ransmayr G, Sgonc R, Lassmann H, Grubeck-Loebenstein B (1996) APP peptides stimulate lymphocyte proliferation in normals, but not in patients with Alzheimer’s disease. Neurobiol Aging 17:541–547
Woiciechowsky C, Schoning B, Lanksch W-R, Volk H-D, Docke W-D (1999) Mechanisms of brain-mediated systemic anti-inflammatory syndrome causing immunodepression. J Mol Med 77:769–780
Wyss-Coray T, Mucke L (2002) Inflammation in neurodegenerative disease—a double-edged sword. Neuron 35:419–432
Yamada K, Kono K, Umegaki H, Aymada K, Iguchi A, Fukatsu T et al (1995) Decreased interleukin-6 level in cerebrospinal fluid of patients with Alzheimer-type dementia. Neurosci Lett 186:219–221
Zhang J, Kong Q, Zhang Z, Ge P, Ba D, He W (2003) Telomere dysfunction of lymphocytes in patients with Alzheimer’s disease. Cogn Behav Neurol 16:170–176
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Richartz-Salzburger, E., Koehler, N. (2009). Decline of Immune Responsiveness: A Pathogenetic Factor in Alzheimer’s Disease?. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_61
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