Neuroinflammation – An Early Event in Both the History and Pathogenesis of Alzheimer’s DiseaseEikelenboom 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
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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Published online: February 13, 2010
Number of Print Pages : 4
Number of Figures : 1, Number of Tables : 0, Number of References : 19
Vol. 7, No. 1-3, Year 2010 (Cover Date: April 2010)
Journal Editor: Nitsch R.M. (Zürich), Hock C. (Zürich)
ISSN: 1660-2854 (Print), eISSN: 1660-2862 (Online)
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