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- W3090637663 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 degeneration in part owing to reduced tau disaggregation, raising the possibility that VCP may represent a therapeutic target for the treatment of AD." @default.
- W3090637663 created "2020-10-08" @default.
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- W3090637663 date "2020-11-20" @default.
- W3090637663 modified "2023-10-17" @default.
- W3090637663 title "Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau" @default.
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- W3090637663 doi "https://doi.org/10.1126/science.aay8826" @default.
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