Abstract
BACKGROUND: Excessive alcohol use has emerged as the strongest modifiable risk factor for the development of Alzheimer's disease (AD), but the underlying neural mechanisms are only beginning to be understood. Recent preclinical work suggests that alcohol consumption may have an impact on many pathologies and phenomena crucial to the development and pathogenesis of AD. However, little attention has been focused on pure tauopathy models to closely examine tau pathogenesis and neuroinflammation within a voluntary alcohol exposure paradigm. METHODS: We exposed a mouse model of pathological tau (pTau), P301S, to a voluntary alcohol paradigm known as drinking-in-the-dark (DID) for 21 days of voluntary daily alcohol consumption. RESULTS: In P301S mice, moderate alcohol consumption contributed to gait disruptions, acceleration of pTau spread, and enhancement of damage-associated microglia. CONCLUSIONS: This work identifies key interactions between alcohol and AD-related phenotypes which set the stage for future investigation into the neurobiological mechanisms behind these interactions.