Adolescent intermittent ethanol exacerbates Aβ with age in the dorsal hippocampus of female TgF344-AD rats.

Background Alcohol misuse increases Alzheimers disease (AD) risk, however the mechanisms linking these conditions are unknown. In rodents, chronic and acute ethanol increases amyloid-[beta] (A[beta]), however those studies have been limited to a single sex or brain region. Objective This study explored how adolescent intermittent ethanol (AIE), alters A[beta] in multiple regions of the brain in female and male TgF344-AD rats as they age. Methods From P28-P58, female and male TgF344-AD rats were administered either water (CON) or 5.0 g/kg ethanol (AIE; 20% ethanol w/v) via intragastric gavage on a 2-day on/off cycle. In Experiment 1, A[beta] was measured in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), piriform cortex (PC), entorhinal cortex (EC), ventral hippocampus (vHPC), and dorsal hippocampus (dHPC) in 6- and 10-month-old rats. In Experiment 2, in vivo microdialysis was used in 3-month-old female rats to measure how ethanol directly modulates A[beta]; levels in the dHPC. Results In the OFC, PC, EC, vHPC, and dHPC, A[beta]40 and A[beta]42 was higher in 6-month-old female TgF344-AD rats compared to males. However, at 10 months A[beta]40 and A[beta]42 levels were only elevated in the dHPC of AIE-treated females, compared to all other groups. An acute ethanol challenge at 3 months selectively evoked a sustained increase in ISF A[beta]40 levels in AIE-treated females. Conclusions In aged females, the dHPC is a region sensitive to ethanol-associated A[beta] pathology. This may be due to disruptions in Aβ clearance in early life, which may have an additive effect on A[beta] aggregation over the lifespan.