There are nearly 7 million Americans with Alzheimer’s disease and it is expected to double to 13.8 million by 2060. Epidemiological studies identify genetic predisposition and aging as the primary risk factors for Alzheimer’s disease.
According to scientists at Scripps Research, Alzheimer’s and AUD share similarly altered gene expression patterns in the brain, suggesting that alcohol use could accelerate Alzheimer’s disease progression. This study —published ahead of print on September 19, 2024, in eNeuro—could help inform future preventative and treatment strategies. The senior author Pietro Paolo Sanna, MD, explains, “We found several cell types specific genes, and particular pathways that are dysregulated in the individuals suffering from Alzheimer’s and alcohol addiction.”
Also note that ‘with the understanding of these dysregulations at the molecular level, we can understand causation of disease and will find therapeutic targets and treatment methods.’
This is the first study to examine differences in gene expression changes between Alzheimer’s disease versus (AUD) and in different populations of human brain cells using single-cell transcriptomics—a method of observing gene expression change within cells by reading the RNA contained in that cellular material. This builds upon previous Sanna lab research published in Nature earlier this year that demonstrated excessive alcohol use accelerates Alzheimer’s in mice genetically predisposed to the disease.
The team then analyzed RNA sequencing data from hundreds of thousands of individual brain cells from 75 patients with different stages of Alzheimer’s disease (early, intermediate, or advanced) and 10 patients without Alzheimer’s to see if changes in gene expression were cell-specific. Next, they contrasted this data to previously published RNA sequencing data from people with AUD.
Both Alzheimer’s and AUD appear to share similar gene expression alterations in the brain, including upregulated inflammatory genes and pathways, perturbed cell signaling and cell death pathways, and perturbed vectors.
“We’ve taken that differential view of two disorders that are known to cause cognitive decline,” says first author Arpita Joshi, Ph.D., a staff scientist in Sanna’s lab at Scripps Research.
Dr. Richard van Nuenen says, “This helps us to understand Alzheimer’s disease in a better way along with its three clinically defined stages and the risk of alcohol intake in Alzheimer’s disease.”
In the future, researchers plan to repeat their analysis using larger gene expression databases from people with AUD, which they hope to be available within the next year.
Joshi explains: “We are eagerly awaiting the release of larger alcohol use datasets so that we can test the robustness of these findings and determine what commonalities hold for both disorders on finer cell type granularity.”
It’s a global approach to fighting diseases on the single-cell level and this will educate you at a molecular and cellular level of the individuals afflicted with Alzheimer’s disease, such as alcoholism and other diseases.
Sanna, Joshi, and Federico Manuel Giorgi of Scripps Research and the University of Bologna were equal authors of the study, “Transcriptional Patterns are Cell Type Specific and Converge Partially with the Effects of Alcohol Use Disorder in Humans’.”
Reference: Joshi A, Giorgi FM, Sanna PP. Transcriptional Patterns in Stages of Alzheimer’s Disease Are Cell-Type-Specific and Partially Converge with the Effects of Alcohol Use Disorder in Humans. eNeuro. 2024;11(10):ENEURO.0118-24.2024. doi:10.1523/ENEURO.0118-24.2024
