Journal Article Ppublish
PubMed: 40409612 DOI: 10.1016/j.alcohol.2025.05.004
Alcohol consumption during early adulthood increases the vulnerability of locus coeruleus neurons and amyloid beta pathology in female APP/PS1 mice.
Alcohol 127:1-9
Authors: Shaydel Engel, Madison Dillerud, Matthew Scalf, Ruth Dobbelmann, Yijuan Du, Anna M Lee, Steven M Graves
Affiliations
- Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
- Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Abstract
Alcohol use disorder is the most common substance misuse disorder and Alzheimer's disease (AD) is the most common neurodegenerative disease. Evidence suggests that alcohol consumption may increase the risk for developing dementia and AD. The locus coeruleus (LC) is a region wherein the impact of alcohol and AD may converge. The LC is a noradrenergic nucleus that is highly vulnerable to degeneration in AD, and loss of LC neurons is associated with increased amyloid beta (Abeta) pathology. The present study examined whether alcohol consumption during early adulthood impacts LC degeneration and Abeta using the APP/PS1 mouse model. Female APP/PS1 mice underwent an eight-week chronic intermittent access (IA) alcohol consumption paradigm followed by twenty-three weeks of abstinence; water-consuming control subjects were run in parallel. APP/PS1 mice that had IA to alcohol showed a 21.9% decrease in the number of LC neurons and a decrease in the length of noradrenergic axons innervating the primary motor cortex. Furthermore, this alcohol induced LC deficit was associated with an increase in Abeta pathology in the primary motor cortex. In contrast to results from female APP/PS1 mice, there were no deficits in axon length and only a 9.4% decrease in the number of LC neurons in non-transgenic female subjects after abstinence from IA to alcohol. Our results demonstrate that alcohol consumption during early adulthood increases the vulnerability of LC neurons to degeneration and exacerbates Abeta pathology in female APP/PS1 mice, providing evidence that a history of alcohol abuse may impact the trajectory and severity of AD.
MeSH
Locus Coeruleus, Neurons, Amyloid Beta-Peptides, Alcoholism, Motor Cortex, Pathology, Axons, Amyloid, Ethanol, Alcohol Drinking