Summary: Even modest consumption of alcohol can accelerate brain atrophy and increase amyloid plaque formation. The findings reveal alcohol consumption can accelerate Alzheimer’s disease pathologies.
Source: Wake Forest University
Alzheimer’s disease is the most common form of dementia, accounting for 60% to 80% of dementia cases, according to the Alzheimer’s Association. While current research suggests alcohol use disorder is a risk factor in Alzheimer’s disease, the impact alcohol use disorder has on Alzheimer’s disease pathology is an area of continued research.
In a new preclinical study, scientists at Wake Forest University School of Medicine showed that even modest amounts of alcohol can accelerate brain atrophy, which is the loss of brain cells, and increase the number of amyloid plaques, which are the accumulation of toxic proteins in Alzheimer’s disease.
The study appears in Neurobiology of Disease.
“These findings suggest alcohol might accelerate the pathological cascade of Alzheimer’s disease in its early stages,” said Shannon Macauley, Ph.D., associate professor of physiology and pharmacology at Wake Forest University School of Medicine.
The study was a collaboration led by Macauley and Jeffrey Weiner, Ph.D., professor of physiology and pharmacology at Wake Forest University School of Medicine, through the medical school’s Alzheimer’s Disease Research Center and Translational Alcohol Research Center.
Using mouse models of Alzheimer’s disease-related pathology, researchers used a 10-week chronic drinking approach where mice were given the choice to drink water or alcohol, mimicking human behavior regarding alcohol consumption. They then explored how voluntary, moderate consumption of alcohol altered healthy brain function and behavior and whether it altered the pathology associated with the early stages of Alzheimer’s disease.
The researchers found that alcohol increased brain atrophy and caused an increased number of amyloid plaques including a greater number of smaller plaques, potentially setting the stage for increased plaque proliferation in later life.
Interestingly, researchers also noted that acute withdrawal of alcohol increased the levels of amyloid-beta, which is a key component of amyloid plaques that accumulate in Alzheimer’s disease.
Further analysis showed that chronic alcohol exposure poorly regulated brain and peripheral metabolism—another way to accelerate Alzheimer’s disease pathology. Macauley previously showed that elevated blood sugar increases amyloid-beta and amyloid plaques.
In the current study, researchers found that even moderate drinking caused elevations in blood sugar and markers of insulin resistance, which increases the risk not only for Alzheimer’s disease but also for other diseases such as type 2 diabetes and cardiovascular disease.
The study also found that moderate alcohol use altered anxiety and dementia-related behaviors.
“These preclinical findings suggest that even moderate consumption of alcohol can result in brain injury,” Macauley said. “Alcohol consumption may be a modifiable risk factor for Alzheimer’s disease and dementia.”
About this alcohol consumption and Alzheimer’s disease research news
Author: Press Office
Source: Wake Forest University
Contact: Press Office – Wake Forest University
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Original Research: Open access.
“Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism in APP/PS1 mice” by Stephen M. Day et al. Neurobiology of Disease
Abstract
Ethanol exposure alters Alzheimer’s-related pathology, behavior, and metabolism in APP/PS1 mice
Epidemiological studies identified alcohol use disorder (AUD) as a risk factor for Alzheimer’s disease (AD), yet there is conflicting evidence on how alcohol use promotes AD pathology. In this study, a 10-week moderate two-bottle choice drinking paradigm was used to identify how chronic ethanol exposure alters amyloid-β (Aβ)-related pathology, metabolism, and behavior.
Ethanol-exposed APPswe/PSEN1dE9 (APP/PS1) mice showed increased brain atrophy and an increased number of amyloid plaques. Further analysis revealed that ethanol exposure led to a shift in the distribution of plaque size in the cortex and hippocampus.
Ethanol-exposed mice developed a greater number of smaller plaques, potentially setting the stage for increased plaque proliferation in later life. Ethanol drinking APP/PS1 mice also exhibited deficits in nest building, a metric of self-care, as well as increased locomotor activity and central zone exploration in an open field test. Ethanol exposure also led to a diurnal shift in feeding behavior which was associated with changes in glucose homeostasis and glucose intolerance.
Complementary in vivo microdialysis experiments were used to measure how acute ethanol directly modulates Aβ in the hippocampal interstitial fluid (ISF). Acute ethanol transiently increased hippocampal ISF glucose levels, suggesting that ethanol directly affects cerebral metabolism. Acute ethanol also selectively increased ISF Aβ40, but not ISF Aβ42, levels during withdrawal.
Lastly, chronic ethanol drinking increased N-methyl-d-aspartate receptor (NMDAR) and decreased γ-aminobutyric acid type-A receptor (GABAAR) mRNA levels, indicating a potential hyperexcitable shift in the brain’s excitatory/inhibitory (E/I) balance. Collectively, these experiments suggest that ethanol may increase Aβ deposition by disrupting metabolism and the brain’s E/I balance.
Furthermore, this study provides evidence that a moderate drinking paradigm culminates in an interaction between alcohol use and AD-related phenotypes with a potentiation of AD-related pathology, behavioral dysfunction, and metabolic impairment.
