AD/PD 2021 | Tau induces neurovascular dysfunction through PSD95-nNOS uncoupling

Accumulation of hyperphosphorylated tau characterizes cerebrovascular abnormalities identified as a preclinical manifestation of Alzheimer’s disease. Costantino Iadecola, MD, Cornell University, New York, NY, describes investigations into the mechanisms underlying these abnormalities to see if tau has a direct impact on the cerebral vasculature. Using mouse models, it was demonstrated that mutated tau suppresses neural activity-induced cerebral blood flow increases. This dysfunction occurred prior to tau pathology and cognitive impairment. The uncoupling was shown to be caused by tau-induced dissociation of neuronal nitric oxide synthase (nNOS) from postsynaptic density 95 (PSD95). This interview took place during the AD/PD™ 2021 conference.