AUTHOR=Tucker Autumn E. , Alicea Pauneto Coral del Mar , Barnett Alexandra M. , Coleman Leon G. TITLE=Chronic Ethanol Causes Persistent Increases in Alzheimer’s Tau Pathology in Female 3xTg-AD Mice: A Potential Role for Lysosomal Impairment JOURNAL=Frontiers in Behavioral Neuroscience VOLUME=16 YEAR=2022 URL=https://www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2022.886634 DOI=10.3389/fnbeh.2022.886634 ISSN=1662-5153 ABSTRACT=
Epidemiological studies have found that heavy alcohol use is associated with increased risk for Alzheimer’s disease (AD), with frequent drinking earlier in adulthood increasing risk. The increases in neuroinflammation featured in both heavy alcohol use and AD may be partially responsible for this link. However, it is unknown if abstinence mitigates this risk. We hypothesized that binge ethanol during mid adult life would persistently increase AD pathology even after prolonged abstinence. Male and female 3xTg-AD mice (APPSwe, tauP301, Psen1tm1Mpm) which feature progressive amyloid (Aβ) and tau pathology, received chronic binge ethanol (5g/kg/day, 5-days-on/2-days-off, i.g.) or water during adulthood (from 5.5 to 9 months of age), followed by abstinence and assessment at 14 months of age. The effects of ethanol on protective AD genes (e.g., APOE and TREM2) as well as proinflammatory genes were measured by PCR. Levels of pathologic tau and Aβ were measured by immunohistochemistry and western blot. Ethanol caused persistent reductions in protective AD genes: APOE (25% reduction, *