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Seed-induced Abeta deposition impairs adult neurogenesis, triggers neurodegeneration and is modulated by microglia under environmental enrichment

Waldkirch, Stephnie and d' Errico, Paolo and Sauer, Jonas-Frederic and Savanthrapadian, Shakuntala and Loreth, Desiree and Katzmarski, Natalie and Bartos, Marlene and Prinz, marco and Meyer-Luehmann, Melanie (2017) Seed-induced Abeta deposition impairs adult neurogenesis, triggers neurodegeneration and is modulated by microglia under environmental enrichment. The EMBO Journal, 37 (2). pp. 167-182. ISSN 0261-41891460-2075

Abstract

Alzheimer´s disease (AD) is characterized by severe neuronal loss as well as the accumulation of amyloid- (Abeta) which ultimately leads to plaque formation. Although a decline of neurogenic capacity in the brain of AD patients and AD mouse models has been reported, our understanding of whether this impairment is specifically altered by Abeta plaques is limited. Here, we find that induced Abeta deposition (Abeta seeding), representing early stages of plaque formation, leads to a dramatic decrease in proliferation and neurogenesis. We further demonstrate that signs of neuronal cell death occur primarily in the vicinity of induced Abeta deposits. Notably, environmental enrichment and voluntary exercise not only revives adult neurogenesis but, most importantly, prevents Abeta seeding by activated, phagocytic microglia cells. Our work expands the current knowledge regarding Abeta seeding and the consequences thereof and attributes microglia an important role in diminishing Abeta seeding by environmental enrichment.

Item Type: Article
Date Deposited: 27 Aug 2019 00:45
Last Modified: 27 Aug 2019 00:45
URI: https://oak.novartis.com/id/eprint/30931

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