The investigators will conduct two studies in parallel: a mouse study to determine the longitudinal growth of amyloid plaques in transgenic mice and a human study to determine the acute effects of antidepressants in human CSF. Dr. Sheline and her co-investigators have demonstrated that antidepressants lower amyloid production in mouse brain in transgenic mice. They now extend the study to determine the effect on amyloid plaque accumulation. In addition they will gather preliminary data on antidepressant effects on human CSF amyloid, a marker of Alzheimer’s disease.
“Citalopram Decreases Amyloid-B Synthesis in Human CSF”
NIH-NINDS, R21AG0390690-01A1 (PI, Sheline)
This project will determine whether compared to placebo, SSRI antidepressants lower the production of Aβ in human CSF.
“Citalopram decreases CSF Aβ: a randomized dose finding trial”
NIH-NINDS, R01AG041502-01A1 (PI, Sheline)
“Synaptic regulation of ERK-mediated amyloid-β metabolism”
NIH-NINDS, R01AG042513 (PI, Cirrito)
Cirrito JR, DiSabato BM, Restivo JL, Verges DK, Goebel WD, Sathyan A, Hayreh D, D’Angelo G, Benzinger T, Yoon H, Kim J, Morris JC, Mintun MA, Sheline YI. Serotonin signaling is associated with lower amyloid-beta levels and plaques in transgenic mice and humans. PNAS, 108:14968-73 (2011).
Sheline YI, West T, Yarasheski K, Swarm R, Jasielec MS, Fisher JR, Ficker WD, Yan P, Xiong C, Frederiksen C, Grzelak MV, Chott R, Bateman RJ, Morris JC, Mintun MA, Lee JM, Cirrito JR. An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice. Sci Transl Med, 10.1126/scitranslmed.3008169 (2014).
Updated March 2016