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.