Serotonergic dysfunction may mediate the relationship between alcohol consumption and Alzheimer’s disease

The impact of Alzheimer’s disease (AD) and its related dementias is rapidly expanding, and its mitigation remains an urgent social and technical challenge. To date there are no effective treatments or interventions for AD, but recent studies suggest that alcohol consumption is correlated with the risk of developing dementia. In a review, data from preclinical, clinical, and epidemiological models was synthesized to evaluate the combined role of alcohol consumption and serotonergic dysfunction in AD, underscoring the need for further research on this topic.
The authors first discuss the limitations inherent to current data-collection methods, and how neuropsychiatric symptoms common among AD, alcohol use disorder, and serotonergic dysfunction may mask their co-occurrence. Additionally, they describe how excess alcohol consumption may accelerate the development of AD via direct effects on serotonergic function, and explore the roles of neuroinflammation and proteostasis in mediating the relationship between serotonin, alcohol consumption, and AD. Lastly, the authors argue for a shift in current research to disentangle the pathogenic effects of alcohol on early-affected brainstem structures in AD.
Source: Pierson SR, Kolling LJ, James TD, Pushpavathi SG, Marcinkiewcz CA. Serotonergic dysfunction may mediate the relationship between alcohol consumption and Alzheimer’s disease. Pharmacol Res. 2024 May;203:107171.