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2023 Alzheimer's Association Research Grant (AARG)

Alcohol Use and APOE Genotype in Alzheimer's Disease Risk

How does chronic alcohol exposure impact Alzheimer’s risk?

Danielle Gulick, Ph.D.
University of South Florida
Tampa, FL - United States


Chronic alcohol exposure can damage brain cells and reduce brain size (volume). People with alcohol use disorder are at increased risk of developing these brain changes, which can contribute to cognitive decline.

Previous studies in mice show chronic alcohol exposure reduces levels of a protein called aldehyde dehydrogenase 2 (ALDH2) in the brain. This protein may also be important for Alzheimer’s. Mice with low levels of ALDH2 have the hallmark brain changes of Alzheimer’s, including beta-amyloid and tau protein accumulation, and problems with cognition.

Other studies show individuals with APOE-e4, a genetic variation that increases the risk of Alzheimer’s in some populations, are at even greater risk of disease if they also have genetic variations in ALDH2. This suggests a link between APOE and ALDH2, but more research is needed to understand the molecular relationship of these proteins.

Research Plan

Dr. Danielle Gulick and colleagues will study the link  between APOE and ALDH2 and how chronic alcohol use might play a role using  genetically-engineered Alzheimer’s-like mice modified to carry Alzheimer’s risk genes and lack ALDH2. They will expose the mice to alcohol during critical periods of brain development: during gestation and during adolescence.

First, Dr. Gulick’s team will monitor the behavior and brain activity of mice who experienced constant alcohol exposure before birth. Next, the researchers will measure beta amyloid and tau levels in brain tissue collected from the mice. Dr. Gulick’s team will perform similar analyses in genetically modified mice who consume alcohol daily for two-week periods as young adults, which will serve as a model of binge drinking behavior. Dr. Gulick’s goal is to determine the types of molecular processes that are most impacted by chronic alcohol exposure.


Findings from this study could uncover how the presence of Alzheimer’s risk genes might change the way the brain responds to alcohol. The study also offers an understanding of how  chronic alcohol exposure early in life affects brain function, particularly in the context of Alzheimer’s.

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