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

11/09/2026

AI Summary

Chronic alcohol consumption is a modifiable risk factor that increases risk and accelerates progression of Alzheimer’s disease.
Alcohol metabolism disrupts acetylation pathways including acetyl-CoA, NAD+ balance, acetyltransferases and sirtuins, promoting abnormal tau acetylation and neurofibrillary tangle formation.
Targeting alcohol-induced acetylation and tau dysregulation may yield therapeutic strategies to prevent or slow Alzheimer’s disease progression.

AI Summary

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.

Basic summary

Neuroscience. 2026 Sep 10:S0306-4522(26)00623-8. doi: 10.1016/j.neuroscience.2026.09.012. Online ahead of print.

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.

PMID:42722128 | DOI:10.1016/j.neuroscience.2026.09.012

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