Gene Study Links Alcohol Addiction to Accelerated Alzheimer’s Transition

Summary: Researchers discovered alcohol use disorder ( AUD) and Alzheimer’s disease ( AD ) exhibit similar patterns of gene dysregulation, hinting that alcohol consumption may hasten Alzheimer’s progression. By analyzing gene expression across specific brain tissue, the crew found shared disruptions in infection, body signaling, and blood vessel features in both disorders.

These findings highlight the potential danger of AD and suggest new therapeutic targets for AUD. The study underscores the need to consider drug’s effect in Alzheimer’s prevention and treatment techniques. Upcoming studies aim to use larger AUD data to verify results.

Important Information:

  • Similar protein regulation in swelling and cell signaling is observed in both AUD and AD.
  • AUD may raise Alzheimer’s development by targeting intersecting chemical pathways.
  • Single-cell RNA scanning reveals that AD and AUD share similar mobile threats.

Origin: Scripps Research Institute

Nearly 7 million Americans have Alzheimer’s disease, and this number is predicted to increase by 2060. Although the most significant risk factors for Alzheimer’s are aging and genetic predisposition, clinical studies suggest that life elements, including alcohol use, may even affect disease beginning and growth.

Now, Scripps Research scientists have shown that Alzheimer’s and&nbsp, alcohol use disorder&nbsp, ( AUD) are associated with similarly altered&nbsp, gene expression patterns&nbsp, in the brain, supporting the idea that alcohol use may promote Alzheimer’s disease progression.

They showed that both AUD and Alzheimer’s are associated with similar gene expression changes in the brain, including upregulation of inflammatory genes and pathways, disruption to cell signaling and cell-death-related pathways, and changes to blood vessel cells. Credit: Neuroscience News

The study, published in&nbsp, eNeuro&nbsp, on September 19, 2024, could inform future preventative and treatment strategies.

” We found several cell-type-specific genes and pathways that are dysregulated in both Alzheimer’s disease and alcohol, which supports the hypothesis that alcohol use disorder can accelerate Alzheimer’s disease progression by impinging on some of the same&nbsp, molecular mechanisms&nbsp, that are affected by Alzheimer’s”, says senior author Pietro Paolo Sanna, MD, a professor in the Immunology and Microbiology Department at Scripps Research.

” By understanding these dysregulations with this level of molecular detail, we can understand what’s causing these diseases, and we can also identify targets that could be used therapeutically”.

This is the first time researchers have used single cell transcriptomics —a method that analyzes gene expression within&nbsp, individual cells&nbsp, by sequencing their RNA—to compare changes associated with Alzheimer’s disease and AUD in different populations of human brain cells.

The study builds upon previously published research in the Sanna lab that showed that&nbsp, excessive alcohol consumption accelerates Alzheimer’s progression&nbsp, in mice that are genetically predisposed to the disease.

To examine cell-specific gene expression changes, the team analyzed RNA sequencing data from hundreds of thousands of individual brain cells from 75 patients with varying stages of Alzheimer’s disease ( early, intermediate or advanced ), and 10 patients without Alzheimer’s.

Then, they compared the Alzheimer’s gene expression data with previously published RNA sequencing data from AUD subjects.

They showed that both AUD and Alzheimer’s are associated with similar gene expression changes in the brain, including upregulation of inflammatory genes and pathways, disruption to&nbsp, cell signaling&nbsp, and cell-death-related pathways, and changes to blood vessel cells.

” What we’ve presented here is a differential analysis of two disorders that cause&nbsp, cognitive decline”, says first author Arpita Joshi, Ph. D., a staff scientist in Sanna’s lab at Scripps Research.

It advances our understanding of Alzheimer’s disease and what the three clinically defined stages of the disease entail, and it emphasizes the importance of considering alcohol use disorder as a risk factor for Alzheimer’s.

In the future, researchers intend to repeat their analysis using larger gene expression databases from people with AUD, which they anticipate will be available in the next year because the study was based on a small sample size for AUD.

We are eagerly awaited by larger alcohol use datasets in order to test the robustness of these findings and examine the similarities between the two conditions with finer cell-type granularity, says Joshi.

” This is a global effort to unravel complex diseases at the single-cell level, which will lead to a better understanding of the molecular and cellular perturbations in individuals with Alzheimer’s disease, alcohol use disorder, and their interactions”.

The study,” Transcriptional Patterns in Alzheimer’s Disease Are Cell-Type-Specific and Partially Convergent with the Effects of Alcohol Use Disorder in Humans,” was co-authored by Federico Manuel Giorgi of Scripps Research and the University of Bologna in addition to Sanna and Joshi.

About this AUD and Alzheimer’s disease research news

Author: Pietro Paolo Sanna
Source: Scripps Research Institute
Contact: Pietro Paolo Sanna – Scripps Research Institute
Image: The image is credited to Neuroscience News

Original Research: Open access.
The research paper” Transcriptional Patterns in Alzheimer’s Disease Stages Are Cell-Type-Specific and Partially Convergent with the Effects of Alcohol Use Disorder in Humans” by Pietro Paolo Sanna and al. eNeuro


Abstract

The effects of alcohol use disorder in humans are both specific to the stages of Alzheimer’s disease and partially converging with one another.

Advances in single-cell technology have enabled the identification and characterization of novel types of brain cells, which in turn have improved our understanding of Alzheimer’s disease ( AD ).

We compare single-nucleus ( sn ) RNA-seq data from the middle temporal gyrus to snRNA-seq data from people with alcohol use disorder ( AUD) and present a thorough analysis of sn RNA-seq data for three stages of AD.

In general, we observed a significant decrease in both the number of inhibitory and number of excitatory neurons, which is in line with previous reports. We identified several AD stages-specific gene expressions and pathway dysregulations.

The highest level of gene expression changes were found in vascular and endothelial leptomeningeal cells. Multiple neuronal cell types, particularly somatostatin and Layer 5 extratelencephalic neurons, showed cell-type-specific neurodegeneration evidence, among others.

Non-neuronal cells, particularly those with intermediate and advanced AD, showed evidence of inflammatory responses.

We observed common perturbations in AD and AUD, particularly in pathways, like transcription, translation, apoptosis, autophagy, calcium signaling, neuroinflammation, and phosphorylation, that imply shared transcriptional pathogenic mechanisms and support the role of excessive alcohol intake in AD progression.

A network of genes that are closely related to intermediate and advanced AD is formed and altered by significant AUD gene markers.

A master regulator analysis of AUD gene markers revealed a significant correlation with advanced AD of transcription factors that have implications for neuroinflammation, neurodegenerative conditions, further supporting the existence of a shared nexus of transcriptional changes between AD and AUD.

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