Dietary Salt, Tau Phosphorylation and Cognitive Impairment


Vascular factors contribute to Alzheimer’s disease, the most common cause of dementia in the elderly. It is characterized by accumulation of amyloid beta in amyloid plaques and hyperphosphorylated tau in neurofibrillary tangles. Dietary salt has emerged as a risk factor for stroke, white matter disease and cognitive impairment, independent of hypertension. A high-salt diet leads to a selective reduction in endothelial nitric oxide, a key mediator of vascular tone in the brain, and is associated with profound cognitive impairment in mice. However, how HSD-induced endothelial dysfunction affects cognitive function is not clear. In particular, considering the potential link between a deficit in endothelial NO and tau phosphorylation, it is conceivable that HSD may promote cognitive impairment through tau phosphorylation.

This research examines the hypothesis that a high-salt diet-caused endothelial dysfunction induces cognitive impairment by suppressing endothelial nitric oxide production. Elucidating how endothelial dysfunction induces cognitive impairment may provide a previously unrecognized mechanism linking vascular health to tau pathology and subsequent cognitive impairment.

Funding to Date



Biomarkers/Diagnostics/Studies of Risk & Resilience, Foundational


Giuseppe Faraco, M.D., Ph.D.

Costantino Iadecola, M.D.

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