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bioRxiv · 10.1101/2025.10.20.683498

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

Day, S. M.·Reitz, N. L.·Savage, L. M.
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Abstract

BackgroundAlcohol 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. ObjectiveThis 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. MethodsFrom 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. ResultsIn 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. ConclusionsIn aged females, the dHPC is a region sensitive to ethanol-associated A{beta} pathology. This may be due to disruptions in A{beta} clearance in early life, which may have an additive effect on A{beta} aggregation over the lifespan.

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Day, S. M., Reitz, N. L., Savage, L. M.. 2025-10-21. Adolescent intermittent ethanol exacerbates Aβ with age in the dorsal hippocampus of female TgF344-AD rats.. https://doi.org/10.1101/2025.10.20.683498

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