An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice
| Autor: | Robert A. Swarm, John C. Morris, Ping Yan, Randall J. Bateman, Chengjie Xiong, Yvette I. Sheline, Mateusz S. Jasielec, Mark A. Mintun, Whitney D. Ficker, Jonathan R. Fisher, John R. Cirrito, Christine Frederiksen, Jin-Moo Lee, Kevin E. Yarasheski, Monica V. Grzelak, Robert Chott, Tim West |
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| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Microdialysis business.industry Serotonin reuptake inhibitor General Medicine Pharmacology Citalopram behavioral disciplines and activities Article Dose–response relationship Endocrinology Cerebrospinal fluid Interstitial fluid Internal medicine mental disorders Antidepressant Medicine Serotonin business medicine.drug |
| Zdroj: | Science Translational Medicine. 6 |
| ISSN: | 1946-6242 1946-6234 |
| Popis: | Serotonin signaling suppresses generation of amyloid-β (Aβ) 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 (SSRI), decreased Aβ in brain interstitial fluid (ISF) 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 pre-existing plaques and reduced the appearance of new plaques by 78%. In healthy human volunteers, citalopram’s effects on Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable-isotope labeling kinetics (SILK), with CSF sampling during acute dosing of citalopram. Aβ 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 Aβ concentrations in the drug-treated group. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD. This study demonstrates key target engagement for future AD prevention trials. |
| Databáze: | OpenAIRE |
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