Impaired adult neurogenesis is an early event in Alzheimer's disease neurodegeneration, mediated by intracellular Aβ oligomers.

ABSTRACT: Alterations of adult neurogenesis have been reported in several Alzheimer's disease (AD) animal models and human brains, while defects in this process at presymptomatic/early stages of AD have not been explored yet. To address this, we investigated potential neurogenesis defects in Tg2576 transgenic mice at 1.5 months of age, a prodromal asymptomatic age in terms of Aβ accumulation and neurodegeneration. We observe that Tg2576 resident and SVZ-derived adult neural stem cells (aNSCs) proliferate significantly less. Further, they fail to terminally differentiate into mature neurons due to pathological, tau-mediated, and microtubule hyperstabilization. Olfactory bulb neurogenesis is also strongly reduced, confirming the neurogenic defect in vivo. We find that this phenotype depends on the for

SUBMITTER: Scopa C 

PROVIDER: S-EPMC7206128 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature