Researchers at Scripps Research and the University of Bologna have recently discovered that the combination of genetic predisposition and alcohol use disorder (AUD) may hasten the progression of Alzheimer’s. The study’s findings elucidate the molecular processes driving memory loss and may have broader ramifications for comprehending and managing Alzheimer’s, irrespective of the consumption of alcohol.
According to a recent study published in eNeuro, mice exposed to periodic high amounts of alcohol showed signs of cognitive loss about two months earlier than they would have otherwise. Ethanol increases the onset of Alzheimer’s disease (AD) by several months or possibly a few years in people with a hereditary predisposition to the disorder.
While there hasn’t been much research on how alcohol affects Alzheimer’s progression, epidemiological studies have indicated that alcohol use disorder may raise the overall risk of dementia development.
The researchers performed an experiment where mice were subjected to recurrent alcohol use over months, simulating the amounts of alcohol exposure reported in people with alcohol use disorder.
They contrasted the behavior of control mice with those with three particular gene mutations linked to an increased risk of Alzheimer’s.
What is the link between dementia & alcohol?
Previous studies have suggested a link between alcohol consumption and brain damage. The National Institute for Health and Care Excellence (NICE) and Alzheimer’s Disease International examined several research studies on the relationship between alcohol use and dementia development.
Both reviews adopted a systematic methodology in which experts assessed the findings of numerous earlier published research investigations.
These studies observed that people who drank heavily or binge drank (consuming a lot of alcohol quickly) had a higher risk of developing Alzheimer’s disease or any other form of dementia than people who drank moderately.
The NICE-evaluated research concentrated on sizable populations of hundreds or even thousands of people, commencing in mid-life (age 40–64). They followed them for more than five years, often far into old age, to examine how long-term behavioral habits could affect dementia risk.
How might alcohol harm the brain?
Brain damage can result from heavy alcohol use over an extended period. Long-term heavy drinkers are more likely to have less white matter in their brains, which aids in signal transmission between various brain regions. It may cause problems with how the brain works.
Additionally, prolonged heavy drinking can lead to thiamine B1 deficiency and Korsakoff’s syndrome, a memory condition that affects short-term memory.
How alcohol and genetic predisposition can accelerate Alzheimer’s onset?
The current study’s findings showed that mice exposed to alcohol gradually lost the ability to acquire and retain spatial patterns, and they started to exhibit these cognitive deficits earlier than mice in the control group.
The researchers discovered cognitive deficits in mice who received alcohol treatment almost two months before the standard period when such abnormalities would appear.
They thoroughly investigated the gene expression in the brains of those mice exposed to alcohol and those that weren’t to comprehend the underlying causes of alcohol use disorder.
They also compared the gene expression profiles of over 100,000 individual cells.
According to the findings, alcohol exposure caused significant changes in gene expression across the prefrontal brain.
The researchers observed increased expression of genes linked to neuronal excitability, neurodegeneration, and inflammation, specifically in the alcohol-exposed animals.
Supporting cells, including astrocytes, microglia, and endothelial cells, also showed abnormal gene expression patterns in reaction to alcohol exposure, indicating that these modifications were not confined to neurons.
Previously, neurons were primarily considered responsible for Alzheimer’s-related responses. Scientists have only recently discovered the involvement of these additional cell types in Alzheimer’s progression.
Alcohol alters gene expression, which may result in memory loss.
The researchers contrasted the gene transcription profiles of alcohol-exposed mice with the control group at different ages and stages of Alzheimer’s but with identical genetic backgrounds.
They found that the alcohol-exposed mice’s gene transcription profiles resembled older mice with more severe cognitive deterioration than mice their age.
Upon comparing the alcohol-exposed mice to the same type of mice at different Alzheimer’s stages (including mice without any impairments and severely compromised mice), the researchers found that alcohol exposure changed the gene expression patterns in a way typically associated with advanced stages.
How can it help in future research?
The first step toward understanding the molecular mechanisms underlying memory loss and creating treatments is to comprehend how gene expression changes in various cell groups throughout Alzheimer’s.
The researchers hypothesize that the gene transcription mechanisms involved in Alzheimer’s development with alcohol use disorder (AUD) may also contribute to the explanation of disease progression without alcohol use.
Although the researchers focused on familial Alzheimer’s in this study, the team plans to investigate whether alcohol usage also affects the incidence and course of sporadic Alzheimer’s in individuals who are not genetically prone to the disease in the future.
References
- Sanna, P.P., Cabrelle, C., Kawamura, T., Mercatelli, D., O’Connor, N., Roberts, A.J., Repunte-Canonigo, V. and Giorgi, F.M., 2023. A history of repeated alcohol intoxication promotes cognitive impairment and gene expression signatures of disease progression in the 3xTg mouse model of Alzheimer’s disease. Eneuro.
- National Institute for Health and Care Excellence, 2015. Dementia, disability and frailty in later life—mid-life approaches to delay or prevent onset. NICE guideline [NG16].
- Prince, M., Albanese, E., Guerchet, M. and Prina, M., 2014. World Alzheimer Report 2014. Dementia and Risk Reduction: An analysis of protective and modifiable risk factors (Doctoral dissertation, Alzheimer’s Disease International).
- Excess alcohol consumption may speed up progression of Alzheimer’s disease. Medical News Daily. https://www.medicalnewstoday.com/articles/excess-alcohol-speeds-up-alzheimers-progression. Published Online: 23rd June, 2023. Accessed: 3rd July, 2023.
- Alcohol and Dementia. Alzheimer’s Society. https://www.alzheimers.org.uk/about-dementia/risk-factors-and-prevention/alcohol. Accessed: 3rd July, 2023.
- Alcohol in Excess Hastens Alzheimer’s Progression. Neuroscience. https://neurosciencenews.com/alcohol-genetics-alzheimers-23448/. Published Online: 12th June, 2023. Accessed: 3rd July, 2023.
