TY - JOUR
T1 - Neuroinflammation - An Early Event in Both the History and Pathogenesis of Alzheimer's Disease
AU - Eikelenboom, Piet
AU - van Exel, Erik
AU - Hoozemans, Jeroen J. M.
AU - Veerhuis, Rob
AU - Rozemuller, Annemieke J. M.
AU - van Gool, Willem A.
PY - 2010
Y1 - 2010
N2 - 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 pro-inflammatory 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. Copyright (C) 2010 S. Karger AG, Basel
AB - 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 pro-inflammatory 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. Copyright (C) 2010 S. Karger AG, Basel
U2 - https://doi.org/10.1159/000283480
DO - https://doi.org/10.1159/000283480
M3 - Article
C2 - 20160456
SN - 1660-2854
VL - 7
SP - 38
EP - 41
JO - NEURODEGENERATIVE DISEASES
JF - NEURODEGENERATIVE DISEASES
IS - 1-3
ER -