Abstract: Kasumov & Chung

 Alcohol-altered brain metabolism in a tauopathy mouse model of Alzheimer’s disease

Drs. Takhar Kasumov (Associate Professor in Pharmaceutical Sciences, NEOMED) and Wilson Chung (Associate Professor in Biological Sciences, Kent State University)

Alzheimer's disease (AD), the leading form of dementia, increasingly affects aging populations. Alcohol consumption accelerates brain aging and AD risk by disrupting epigenetic modifications, including histone and tau acetylation, associated with phosphorylated tau (pTau) accumulation. It may worsen AD by impairing glucose metabolism and depleting NAD+, essential for protein deacetylation. Although alcohol alters histone acetylation and increases pTau in rodents, the precise mechanisms remain unclear.

This study utilizes the htau mouse model, an Aβ-independent tauopathy model, with stable isotope flux and ChIP assays to assess alcohol-induced disruptions in brain histone and tau acetylation, and their impact on tau pathology and cognition. We hypothesize alcohol accelerates tauopathy through histone acetylation–mediated transcriptional changes and impaired tau degradation.

Six-month-old htau mice will receive intermittent alcohol or water for four months. Aim 1 investigates whether alcohol disrupts histone acetylation via glucose metabolism impairment and reduces H4K16ac–mediated autophagy. Aim 2 evaluates tau and acetylated tau turnover and examines if NAD+ depletion contributes to increased tau acetylation.

This collaborative effort aims to uncover novel mechanisms underlying alcoholic AD.