Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E

Article

关键词: CEREBROSPINAL-FLUID;    SENILE PLAQUES;    HEAD-INJURY;    DISEASE;    IMMUNOREACTIVITY;    EXPRESSION;    DOMAIN;    CELLS;    ONSET;    BRAIN;   

DOI  :  10.1038/42257

来源: SCIE

【 摘 要 】

A role for beta-amyloid precursor protein (beta-APP) in the development of Alzheimer's disease has been indicated by genetics', and many conditions in which beta-APP is raised have been associated with an increased risk of Alzheimer's disease or an Alzheimer's-like pathology(2-4). Inflammatory events may also contribute to Alzheimer's disease(5), Here we investigate whether a secreted derivative of beta-APP (sAPP-alpha) can induce inflammatory reactions in microglia, which are brain cells of monocytic lineage. We found that treatment with sAPP-alpha increased markers of activation in microglia and enhanced their production of neurotoxins. The ability of sAPP-alpha to activate microglia was blocked by prior incubation of the protein with apolipoprotein E3 but not apolipoprotein E4, a variant associated with an increased risk for Alzheimer's(6). A product of amyloidogenic beta-APP processing (sAPP-beta) also activated microglia. Because sAPP-beta is deficient in the neuroprotective activity shown by sAPP-alpha, our results indicate that increased amyloidogenic processing could adversely affect the balance of sAPP activities that determine neuronal viability.

【 授权许可】

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