Induction of Alzheimer's disease pathology by early-life stress

BioRxiv : the Preprint Server for Biology
T. TanakaHaruo Okado


Alzheimer's disease (AD), a progressive neurodegenerative disorder, is a serious social problem. Recently, several early-life factors have been associated with an increased risk of a clinical diagnosis of AD. In the present study, we investigated the involvement of early-life stress in AD pathogenesis using heterozygous APP mutant mice (AppNL-G-F/wt) and wild-type (Appwt/wt) mice. Maternal separation was used as an animal paradigm for early-life stress. We found that stressed Appwt/wt mice showed narrowing of vessels and decreased pericyte coverage of capillaries in prefrontal cortex, while stressed AppNL-G-F/wt mice showed impairment of place memory, and earlier formation of A{beta} plaques and disruption of the blood-brain barrier than non-stressed AppNL-G-F/wt mice. We detected severe activation of microglia in the stressed AppNL-G-F/wt mice and stressed Appwt/wt mice. In the earlier stage, we detected morphological change and functional change in microglia in the stressed AppNL-G-F/wt mice and stressed Appwt/wt mice, and also detected morphological change in the microglia in the non-stressed AppNL-G-F/wt mice. Therefore, we hypothesize that activated microglia induced by the combination of maternal separation and APP mutati...Continue Reading

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