PRENATAL ENVIRONMENTAL RISK FACTORS FOR ALZHEIMER’S DISEASE: MATERNAL ALCOHOL INTAKE, CIRCADIAN RHYTHM DISRUPTIONS, AND THE ASIAN GLOW EFFECT.

Fetal alcohol spectrum disorders (FASD), often undiagnosed, increase the risk of Alzheimer's Disease (AD). Prenatal alcohol exposure (PAE) and disrupted maternal circadian rhythms (CDs) may synergistically worsen neurodevelopmental impairments. We hypothesize that acetaldehyde accumulation, due to reduced ALDH2 activity, contributes to the PAE-AD link. Pregnant mice (C57BL/6 and ALDH2 variants) received alcohol or water via drinking in the dark, under normal or disrupted light cycles. Offspring were assessed for early reflexes, ultrasonic vocalizations (UVs), and adult behavior and molecular AD markers. Alcohol-exposed dams consumed more fluid, especially in the CD group. In C57BL/6 mice, maternal CDs exacerbated PAE effects: impaired reflexes, growth restriction, and altered UVs. At five months old, the offspring showed long-term impairments: weak responses to both novelty (marble burying) and auditory cues (startle), memory deficits (RAW), and increased anxiety (open field); hallmarks of AD. Preliminary data suggest greater early deficits in mice with lower ALDH2 activity. PAE and maternal CDs significantly impact neurodevelopment, leading to long-term behavioral deficits and AD risk factors, potentially mediated by acetaldehyde