RECENT research has revealed that alcohol use disorder (AUD) and Alzheimer’s disease (AD) share significant patterns of gene dysregulation, suggesting that alcohol consumption may accelerate the progression of Alzheimer’s.
This study, conducted by researchers at Scripps Research, presents critical evidence that AUD could act as a risk factor for AD, impacting both inflammation and cellular signalling pathways in the brain. By focusing on molecular similarities, this research opens avenues for novel therapeutic strategies and highlights the importance of addressing alcohol consumption in Alzheimer’s prevention and treatment.
To explore these associations, researchers employed single-cell RNA sequencing, analysing gene expression in individual brain cells. This method allowed for detailed insights into cellular disruptions across varying AD stages and AUD cases. The study examined RNA sequencing data from hundreds of thousands of brain cells, including 75 patients across early, intermediate, and advanced stages of Alzheimer’s, compared with data from patients with AUD. Findings revealed that both disorders exhibit overlapping gene expression alterations, particularly in genes related to inflammation, cellular signalling, apoptosis, and blood vessel function. The analysis indicated a significant loss of inhibitory and excitatory neurons, with distinct dysregulation in cell types like endothelial cells and vascular leptomeningeal cells, particularly evident in advanced AD stages. Further analysis using “master regulator” markers showed transcriptional changes common to both disorders, suggesting that excessive alcohol intake may indeed contribute to AD pathology through shared molecular mechanisms.
The implications of these findings for clinical practice are substantial, as they underscore AUD as a modifiable risk factor for Alzheimer’s disease. Recognising AUD’s potential to hasten AD progression could prompt new prevention strategies focused on limiting alcohol consumption, particularly among at-risk populations. Additionally, this research highlights specific gene targets, such as those involved in neuroinflammation and cell death, that could serve as potential therapeutic targets for both AUD and AD. Future research aims to expand these findings by utilising larger datasets for AUD to confirm these associations and investigate further molecular details. Such studies will enhance our understanding of the genetic and cellular interplay between AUD and AD, helping to guide interventions aimed at slowing cognitive decline in Alzheimer’s patients.
Reference
Joshi A et al. 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.
