Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau.

ABSTRACT: Neurodegeneration in Alzheimer's disease (AD) is closely associated with the accumulation of pathologic tau aggregates in the form of neurofibrillary tangles. We found that a p.Asp395Gly mutation in VCP (valosin-containing protein) was associated with dementia characterized neuropathologically by neuronal vacuoles and neurofibrillary tangles. Moreover, VCP appeared to exhibit tau disaggregase activity in vitro, which was impaired by the p.Asp395Gly mutation. Additionally, intracerebral microinjection of pathologic tau led to increased tau aggregates in mice in which p.Asp395Gly VCP mice was knocked in, as compared with injected wild-type mice. These findings suggest that p.Asp395Gly VCP is an autosomal-dominant genetic mutation associated with neurofibrillary degenerat

SUBMITTER: Darwich NF 

PROVIDER: S-EPMC7818661 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature