Myelin dysfunction drives amyloid-β deposition in models of Alzheimer's disease.

ABSTRACT: The incidence of Alzheimer's disease (AD), the leading cause of dementia, increases rapidly with age, but why age constitutes the main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and the structural integrity of myelin sheaths¹, the latter of which is associated with secondary neuroinflammation^2,3. As oligodendrocytes support axonal energy metabolism and neuronal health^4-7, we hypothesized that loss of myelin integrity could be an upstream risk factor for neuronal amyloid-β (Aβ) deposition, the central neuropathological hallmark of AD. Here we identify genetic pathways of myelin dysfunction and demyelinating injuries as potent drivers of amyloid deposition in mouse models of AD. Mechanistically, myelin dysfunction causes the

SUBMITTER: Depp C 

PROVIDER: S-EPMC10247380 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature