Tau induces PSD95-neuronal NOS uncoupling and neurovascular dysfunction independent of neurodegeneration.

ABSTRACT: Cerebrovascular abnormalities have emerged as a preclinical manifestation of Alzheimer's disease and frontotemporal dementia, diseases characterized by the accumulation of hyperphosphorylated forms of the microtubule-associated protein tau. However, it is unclear whether tau contributes to these neurovascular alterations independent of neurodegeneration. We report that mice expressing mutated tau exhibit a selective suppression of neural activity-induced cerebral blood flow increases that precedes tau pathology and cognitive impairment. This dysfunction is attributable to a reduced vasodilatation of intracerebral arterioles and is reversible by reducing tau production. Mechanistically, the failure of neurovascular coupling involves a tau-induced dissociation of neuronal nitric oxide syntha

SUBMITTER: Park L 

PROVIDER: S-EPMC7896353 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature