Alcohol-induced dysregulation of tau and acetylation pathways in the pathogenesis of Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose global prevalence is rapidly increasing, highlighting the urgent need to identify modifiable risk factors. Chronic alcohol consumption has emerged as one such significant factor contributing to the risk and progression of AD. Importantly, alcohol metabolism impacts cellular acetylation pathways, creating an environment that promotes protein dysregulation and disrupts cellular functions. Among these alterations, tau acetylation has garnered attention as a crucial post-translational modification that accelerates tau pathology, impairs tau clearance, and facilitates the formation of neurofibrillary tangles (NFTs), the key hallmarks of AD. Growing evidence indicates that chronic alcohol consumption leads to disruptions in acetyl-CoA homeostasis, NAD+ pathways, dysregulation of acetyltransferase, sirtuin activity, and epigenetic aberrations promoting abnormal tau acetylation and neurodegeneration. Thus, understanding the molecular mechanisms that link alcohol consumption, acetylation dysregulation, and tau pathology has significant therapeutic potential in AD treatment.