Moderate alcohol intake worsens the pathology of Alzheimer’s disease

Even modest drinking may accelerate the key characteristics of Alzheimer’s disease progression, according to groundbreaking research from Wake Forest University Medical School. The study was published in February 2023 Neurobiology of Diseasesilluminates how alcohol consumption affects the brain’s vulnerability to this devastating neurodegenerative condition.

Using a complex mouse model that mimics Alzheimer’s disease, researchers found evidence that moderate alcohol intake increases brain atrophy, alters amyloid plaques, and disrupts brain and surrounding metabolism—all key factors in Alzheimer’s disease.

Alcohol produces more, smaller amyloid wood plaques

The research team led by Shannon Macauley and Jeffrey Weiner adopted a 10-week paradigm of voluntary drinking, where mice can choose between water or alcohol. This approach closely reflects human drinking behavior and provides insights into how moderate drinking affects brain health.

“These findings suggest that alcohol may accelerate the pathological cascade of Alzheimer’s disease at its early stages,” said Shannon Macauley, PhD, associate professor of physiology and pharmacology at Wake Forest University School of Medicine.

Although alcohol-exposed mice did not show a sharp increase in overall amyloid burden, they both present more smaller plaques in the cortex and hippocampus, which was severely affected in Alzheimer’s disease. This shift in plaque size distribution may create multiple sites for future plaque proliferation, thus laying the foundation for accelerating disease progression.

Metabolic disruption: a key pathway to disease

Perhaps most striking is the profound effect of alcohol on the metabolism of the brain and the entire body. Showing alcoholic mice:

• Increased glucose intolerance during glucose tolerance test
• Increased plasma glucose levels
• Abnormal feeding methods for interruption of day/night diet cycles
• Acutely increase glucose levels of brain fluid

These metabolic interferences are particularly important because Dr. Macauley’s previous research showed that elevated blood sugar increases amyloid beta production and plaque formation. Current findings suggest that alcohol consumption may promote the pathology of Alzheimer’s disease through metabolic dysfunction, thus establishing links to alcohol use, diabetes risk factors, and neurodegeneration.

Selective effect on amyloid β during extraction

Using advanced microdialysis techniques that measure brain chemicals in real time, the researchers discovered another interesting mechanism: alcohol withdrawal selectively increases the levels of amyloid β40 (Aβ40), but there is no higher toxic amyloid β42 (Aβ42) (Aβ42) in the interstitial fluid of the brain.

This finding suggests that in many drinking modes, repeated drinking and withdrawal cycles may lead to Alzheimer’s disease through different molecular pathways, which can promote the progression of Alzheimer’s disease even at moderate levels of consumption.

Behavioral changes reflect symptoms of Alzheimer’s

The study also documented behavioral changes in alcohol-drinking mice in Alzheimer’s patients. These mice show:

Motor activity and central regional exploration were added in open field tests, indicating overactive or impulsive behavior. They also showed poor nesting ability, a mouse behavior similar to the self-care deficit that is frequently present in Alzheimer’s disease. These behavioral changes occur despite moderate alcohol intake.

“These preclinical findings suggest that even moderate consumption of alcohol can lead to brain damage,” Macauley said. “Alcohol consumption may be a modifiable risk factor for Alzheimer’s disease and dementia.”

Impact on public health

The study has significant public health implications, challenging the notion that moderate drinking is not harmful or may be beneficial to brain health. With Alzheimer’s disease affecting about 6 million Americans, it is expected to triple by 2050, understanding the risk factors that can be changed has become increasingly important.

Although human studies are needed to confirm these findings, the study suggests that even moderate alcohol intake can lead to brain vulnerability