Beta-amyloid levels are associated with Alzheimer’s Disease lesions. One therapeutic strategy has been to reduce amyloid-β levels to limit its accumulation. Since it is known that amyloid-β metabolism can be regulated by different neurotransmitter receptors, the authors studied the effects of serotonin signaling on brain amyloid-β levels and plaques in both humans and a mouse model of Alzheimer’s disease. In mice, amyloid-β levels were decreased by 25% in brain interstitial fluid following administration of serotonin reuptake inhibitor (SSRI) antidepressants. Chronic treatment with the SSRI antidepressant citalopram, caused a 50% reduction in plaque levels in mouse brain. To test whether serotonin signaling could impact amyloid-β plaques in humans, the authors compared brain amyloid load in cognitively normal elderly participants who were exposed to antidepressant drugs within the past 5 years to participants who were not. The majority of subjects had been treated with SSRIs. Antidepressant-treated participants had significantly less amyloid load as measured by positron emission tomography imaging. Cumulative time of antidepressant use within the 5 year period preceding the scan correlated with less plaque load. The authors suggest that serotonin signaling is associated with less amyloid-β accumulation in cognitively normal individuals.
Cirrito JR et al., Serotonin signaling is associated with lower amyloid-β levels and plaques in transgenic mice and humans. Proc. Natl. Acad. Sci. USA 108: 14968-14973 (2011).

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