Anti-Depressant Drugs and Alzheimer’s: A Surprising Relationship
Anti-Depressant Drugs and Alzheimer’s: A Surprising Relationship
Most of our blogs emphasize treatments that directly affect the mechanisms that induce Alzheimer’s disease (AD). However, recent research into the use of anti-depressant drugs and their relationship to AD has provided some interesting results. Namely, administration of escitalopram seems to reduce deposition of amyloid-ꞵ42, which could, in theory, slow the onset or progression of AD.
Escitalopram belongs to a drug class called Selective Serotonin Reuptake Inhibitors (SSRIs) and is one of many similar molecules that are frequently used to treat depression by up-regulating serotonin signaling. Previous research on SSRIs in animal models found that increased serotonin signaling was associated with reduced amyloid-ꞵ42 levels, leading investigators to study its possible benefits for use in older adults with AD.
The current study, a clinical trial, administered escitalopram under 4 conditions: 20 mg/day for 2 weeks, 20 mg/day for 8 weeks, 30 mg/day for 8 weeks, and placebo to cognitively normal older adults to see if it affected amyloid-ꞵ42 burden during that time frame. The treatment groups, on average, experienced a 6.0% (± 1.2%) reduction in CSF levels of amyloid-ꞵ42 while the placebo group experienced a 3.5% (± 2.2%) increase in amyloid-ꞵ42 levels in the CSF. These results suggest that increased serotonin signaling decreases amyloid burden by the activation of a signaling pathway that ends in the production of α-secretase, which suppresses Aꞵ42 generation. This is very important because the degree to which Aꞵ42 produces plaques and impairs neuronal function is dependent upon the concentration of Aꞵ42 present. In animal models, reductions of 10-25% in overall interstitial fluid Aꞵ42 concentrations significantly reduced plaque deposition.
While those in the treatment group of the current study did not see reductions in the 10-25% range, they did see reductions in comparison to the placebo group who actually had an increase in Aꞵ42, meaning that it is possible that SSRI administration may become a preventative strategy to reduce the initiation or progression of AD. However, we first need to determine if reductions in CSF Aꞵ42 correlate to reductions in plaque formation rate in humans, as was shown in rats. On the bright side, many people already use SSRIs regularly so in terms of possible treatment options, this one is very safe and accessible, but only time will tell.
Sources:
Sheline, Y. I., Snider, B. J., Beer, J. C., et al. Effect of escitalopram dose and treatment duration on CSF Aꞵ levels in healthy older adults [Internet]. Neurology. 2020. Available from: https://n.neurology.org/content/95/19/e2658?sso=1&sso_redirect_count=1&oauth-code=AtOok5tDWVPGT3Tmk7Na0iVfQN-vP7YljIOYAQ7VLe8
Cirrito, J. R., Disabato, B. M., Restivo, J. L., et al. Serotonin signaling is associated with lower amyloid-ꞵ levels and plaques in transgenic mice and humans [Internet]. Proceedings of the National Academy of Science of the United States of America. 2011. Available from: https://www.pnas.org/content/108/36/14968