期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 6, 期 236, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.3008169
关键词
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资金
- NIH [R01 AG042513, R21 NS082529, R01 NS067905]
- Washington University Hope Center for Neurological Diseases
- Washington University Biomedical Mass Spectrometry Resource [P41 GM103422, P60 DK020579, P30 DK056341]
- [R21 AG03969002]
- [R01 AG04150202]
Serotonin signaling suppresses generation of amyloid-beta (A beta) in vitro and in animal models of Alzheimer's disease (AD). We show that in an aged transgenic AD mouse model (APP/PS1 plaque-bearing mice), the antidepressant citalopram, a selective serotonin reuptake inhibitor, decreased A beta in brain interstitial fluid in a dose-dependent manner. Growth of individual amyloid plaques was assessed in plaque-bearing mice that were chronically administered citalopram. Citalopram arrested the growth of preexisting plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram's effects on A beta production and A beta concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable isotope labeling kinetics, with CSF sampling during acute dosing of citalopram. A beta production in CSF was slowed by 37% in the citalopram group compared to placebo. This change was associated with a 38% decrease in total CSF A beta concentrations in the drug-treated group. The ability to safely decrease A beta concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials.
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