Document Type
Article
Publication Date
3-23-2025
Abstract
Background: Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of alcohol feeding to AD mice have utilized young mice and delivered alcohol in drinking water without controlling nutritional intake.
Objective: To study the impact of Lieber-DeCarli (LDC) liquid alcohol diet, which balances nutritional intake, on AD pathology of aged Tg2576 and wild-type (WT) mice, which is unexplored.
Methods: 13-month-old male and female Tg2576 or WT mice were fed LDC diet (5% ethanol or control) for six weeks (n = 11-13/group). Exploration (open-field test) and spatial reference memory (Y-maze test) were assessed after six weeks, and brains and livers were studied for Aβ levels, and Aβ synthesis and transport proteins (APP and LRP-1). Neuroinflammation, blood–brain barrier function, and synaptic health were studied using immunoassays.
Results: LDC alcohol feeding significantly reduced survival (p < 0.05) and spatial memory (p < 0.05) in Tg2576 mice, but not in WT mice. Alcohol feeding increased (p < 0.001) insoluble endogenous mouse Aβ1-42 and reduced microgliosis (p < 0.05) in Tg2576 mice brains, but not in WT mice. LDC alcohol feeding to Tg2576 mice caused mild liver injury, and important amyloidosis-relevant hepatic proteins (LRP-1 and APP) were largely unaltered. However, brain Aβ and microgliosis were positively correlated (p < 0.05) with serum alanine aminotransferase, a marker of liver injury, in Tg2576 mice.
Conclusion: Chronic alcohol intake, resulting in mild liver injury, caused modest but significant AD-relevant changes in aged Tg2576 mice, which correlated with liver injury; the latter suggests significant liver-brain crosstalk in an AD model of moderate alcohol intake.
Recommended Citation
Chandrashekar DV, Jagadeesan N, Abdullah T, Chang R, Steinberg RA, Sanchez F, Khal E, Yang J, Cribbs DH, Han D and Sumbria RK (2025) Effect of chronic alcohol feeding using the Lieber-DeCarli diet on Alzheimer’s disease pathology in Tg2576 mice. Front. Aging Neurosci. 17:1526571. https://doi.org/10.3389/fnagi.2025.1526571
Supplementary material
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The authors
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This work is licensed under a Creative Commons Attribution 4.0 License.
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Comments
This article was originally published in Frontiers in Aging Neuroscience, volume 17, in 2025. https://doi.org/10.3389/fnagi.2025.1526571