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Vol. 7, No. 1-3, 2010
Issue release date: April 2010
Neurodegenerative Dis 2010;7:38–41

Neuroinflammation – An Early Event in Both the History and Pathogenesis of Alzheimer’s Disease

Eikelenboom P. · van Exel E. · Hoozemans J.J.M. · Veerhuis R. · Rozemuller A.J.M. · van Gool W.A.
aDepartment of Neurology, Academic Medical Center, University of Amsterdam, Departments of bPsychiatry, cPathology, and dClinical Chemistry and Alzheimer’s Center, VU University Medical Center, Amsterdam, The Netherlands

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Background: About hundred years ago, Oskar Fischer proposed that the senile plaques are the consequence of the deposition of a foreign substance that could induce an inflammatory response leading to an abnormal neuritic response of the surrounding neurons. Objectives: To show that the interest in inflammation in Alzheimer’s disease (AD) is not only an early event in the history of AD but that inflammation is also an early event in the pathogenesis of AD. Methods: Evaluation of the neuropathological, epidemiological and genetic evidence for a role of inflammation early in the pathogenesis of AD. Results: Neuropathological studies show presence of activated microglia and inflammation-related mediators in the cerebral neocortex of autopsied patients with a low Braak stage for AD pathology. Prospective population-based cohort studies indicate that higher serum levels of acute phase proteins predict dementia. On a genetic level, it was found that the production capacity of proinflammatory cytokines after stimulation with lipopolysaccharide (a process that is under strong genetic control) is higher in offspring with a parental history of late-onset AD. Conclusion: Neuropathological studies show that a neuroinflammatory response in the cerebral neocortex parallels the early stages of AD pathology and precedes the late stage, tau-related pathology. Epidemiological and genetic studies indicate that systemic markers of the innate immunity are risk factors for late-onset AD.

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  1. Fischer O: Miliare Nekrosen mit drusigen Wucherungen der Neurofibrillen, eine regelmässige Veränderung der Hirnrinde bei seniler Demenz. Monatsschr Psychiatr Neurol 1907;22:361–372.

    External Resources

  2. Fischer O: Die presbyofrene Demenz, deren anatomischen Grundlage und klinische Abgrenzung. Z Ges Neurol Psychiatr 1910;3:371–471.

    External Resources

  3. Eikelenboom P, Veerhuis R, Scheper W, Rozemuller AJM, van Gool WA, Hoozemans JJM: The significance of neuroinflammation in understanding Alzheimer’s disease. J Neural Transm 2006;113:1685–1695.
  4. Fassbender K, Walter S, Kühl S, Landmann R, Ishii K, Bertsch T, Stalder K, Muelhauser F, Liu Y, Ulmer AJ, Rivest T, Lentschat T, Gulbins E, Jucker M, Staufenbiel M, Brechtel K, Walter J, Multhaup G, Penke B, Adachi Y, Hartmann T, Beyreuther K: The LPS receptor (CD14) links innate immunity with Alzheimer’s disease. FASEB J 2004;18:2003–2005.
  5. Hoozemans JJM, Veerhuis R, Rozemuller JM, Eikelenboom P: Neuroinflammation and regeneration in early stages of Alzheimer’s disease pathology. Int J Dev Neurosci 2006;24:157–165.
  6. Webster B, Hansen L, Adame A, Crews L, Torrance M, Thal L, Masliah E: Astroglial activation of extracellular-regulated kinase in early stages of Alzheimer’s disease. J Neuropathol Exp Neurol 2006;65:142–151.
  7. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW: Incipient Alzheimer’s disease: microarray correlation reveal major transcriptional and tumor supressor responses. Proc Natl Acad Sci USA 2004;101:2713–2718.

    External Resources

  8. Parachikova A, Agadjanyan MG, Cribss DH, Blurton-Jones M, Perreau, Rogers J, Beach TG, Cotman CW: Inflammatory changes parallel the early stages of Alzheimer disease. Neurobiol Aging 2007;28:1821–1833.
  9. Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB: In vivo-measurement of activated microglia in dementia. Lancet 2001;358:461–467.
  10. Okello A, Edison P, Archer HA, Turkheimer FE, Kennedy J, Bullock R, Walker Z, Kennedy A, Fox N, Rossor M, Brooks DJ: Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 2009;72:56–62.
  11. Schmidt R, Schmidt H, Curb JD, Masaki K, White LR, Launer LJ: Early inflammation in dementia: a 25-years follow-up of the Honolulu-Asia Aging Study. Ann Neurol 2002;52:168–174.
  12. Yaffe K, Lindquist K, Penninx BWH, Simsonsick EM, Pahor M, Krichchevsky S, Launer L, Kuller L, Rubin S, Harris T: Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology 2003;61:76–80.
  13. Dik MG, Jonker G, Hack CE, Smit JH, Comijs HC, Eikelenboom P: Serum inflammatory proteins and cognitive decline in older persons. Neurology 2005;64:1371–1377.
  14. Porcellini E, Davis EJ, Chiappelli M, Ianni E, Di Stefano G, Forti P, Ravaglia G, Licastro F: Elevated plasma levels of α1-antichymotrypsin in age-related cognitive decline and Alzheimer’s disease: a potential therapeutic target. Curr Pharm Des 2008;14:2659–2664.
  15. Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S: Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 2007;128:92–105.
  16. Fernandez F, Nikolic WV, Obregon D, Rrapo E, Town T, Tan J: Inflammaging as a prodrome to Alzheimer’s disease. J Neuroinflammation 2008;5:51.
  17. de Craen AJ, Posthuma D, Remarque EJ, van den Biggelaar AH, Westendorp RGJ, Boomsma DI: Heritabili estimates of the innate immunity: an extended twin study. Genes Immun 2005;6:167–170.
  18. van Exel E, Eikelenboom P, Comijs H, Frohlich M, Smit JH, Stek ML, Scheltens P, Eefsting JE, Westendorp RGJ: Vascular factors and markers of inflammation in offspring with a parental history of late-onset Alzheimer’s disease. Arch Gen Psychiatry 2009;66:1263–1270.
  19. Eikelenboom P, van Gool WA: Neuroinflammatory perspectives on the two faces of Alzheimer’s disease. J Neural Transm 2004;113:1685–1695.

    External Resources

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