Neuroinflammation - an early event in both the history and pathogenesis of Alzheimer's disease.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Eikelenboom
Piet
P
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. p.eikelenboom@ggzingeest.nl
van Exel
Erik
E
Hoozemans
Jeroen J M
JJ
Veerhuis
Rob
R
Rozemuller
Annemieke J M
AJ
van Gool
Willem A
WA
D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000266:history*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004660:Encephalitis / Q000209:etiology* / Q000473:pathology*; D049672:History, 19th Century; D049673:History, 20th Century; D006801:Humans; D008954:Models, Biological; D019579:Neocortex / Q000473:pathology*
D016229:Amyloid beta-Peptides