New research revealed that in mice genetically predisposed to Alzheimer's, exposure to intoxicating amounts of alcohol accelerated cognitive decline.
To conduct the study, published on June 12 in eNeuro, scientists from Scripps Research and the University of Bologna exposed Alzheimer's prone mice to an intoxicating level of alcohol vapor intermittently for several months, which is similar to what a person with alcohol use disorder (AUD) experiences.
Control rodents also had a genetic predisposition to Alzheimer's disease but were not exposed to alcohol.
The team found that mice exposed to alcohol began to show cognitive decline two months earlier than the alcohol-free rodents. Specifically, the mice showed a reduced ability to learn and remember spatial patterns in tests.
When researchers examined genetic patterns, they found that rodents exposed to intoxicating levels of alcohol had gene expression signatures more like older mice with advanced Alzheimer's rather than younger mice with early-stage disease. This finding suggests that alcohol may promote transcriptional changes consistent with the progression of Alzheimer's.
In addition, the team discovered that alcohol was associated with changes in the expression of genes in the prefrontal cortex linked to neurodegeneration, neuronal excitability, and inflammation. And these changes appeared not only in neurons but also in astrocytes, microglia, and endothelial cells.
"This is interesting because it used to be thought that neurons were the ones carrying out all the responses associated with Alzheimer's disease, and only recently have these cell types been recognized as having a role in Alzheimer's pathogenesis," says co-lead author Federico Manuel Giorgi, Ph.D., a professor of Computational Genomics at the University of Bologna, in a news release.
The scientists speculate that these gene transcription pathways involved in alcohol-related Alzheimer's progression may offer clues as to how the disease progresses even without alcohol exposure.
Co-lead author Pietro Paolo Sanna, M.D., a professor of Immunology and Microbiology at Scripps Research, explains, "The mechanisms of progression that this dataset will uncover may apply to Alzheimer's in general, even without alcohol. Ultimately, this gene expression analysis will identify key regulatory genes that drive Alzheimer's progression."
To build on these findings, the scientists plan to investigate whether alcohol use affects the onset and progression of Alzheimer's in mice not genetically prone to Alzheimer's disease.