Pathology-Specific Modulation of Corticostriatal Circuitry by Chronic Alcohol Consumption in Alzheimer's Disease Mouse Models.

ABSTRACT: Chronic alcohol use is a major modifiable risk factor for Alzheimer's disease (AD), yet the mechanisms by which it modulates AD pathophysiology remain unclear. Here, we examined circuit-level and pathological changes in two distinct AD mouse models, humanized Aβ knock-in (hAPP-KI) (Aβ-driven) and PS19 (tau-driven), subjected to a chronic intermittent alcohol exposure paradigm. In hAPP-KI mice, alcohol increased Aβ accumulation and excitatory transmission in the medial prefrontal cortex (mPFC) while reducing corticostriatal transmission and striatal cholinergic output. These alterations were accompanied by enhanced recruitment of microglia around Aβ plaques. In contrast, alcohol-exposed PS19 mice displayed elevated mPFC-to-dorsomedial striatum (DMS) glutamatergic transmission and increased

SUBMITTER: Huang Y 

PROVIDER: S-EPMC12393428 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature