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Sci Transl Med. 2014 May 14;6(236):236re4. doi: 10.1126/scitranslmed.3008169.

An antidepressant decreases CSF Aβ production in healthy individuals and in transgenic AD mice.

Author information

1
Departments of Psychiatry, Radiology, and Neurology, University of Pennsylvania, Philadelphia , PA 19104, USA. sheline@mail.med.upenn.edu.
2
C2N Diagnostics LLC, St. Louis, MO 63110, USA.
3
Department of Medicine, Washington University, St. Louis, MO 63110, USA.
4
Department of Anesthesiology, Washington University, St. Louis, MO 63110, USA.
5
Department of Biostatistics, Washington University, St. Louis, MO 63110, USA.
6
Department of Neurology, Washington University, St. Louis, MO 63110, USA.
7
Department of Biostatistics, Washington University, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University Medical Center, St. Louis, MO 63110, USA.
8
Department of Surgery, Washington University, St. Louis, MO 63110, USA.
9
Department of Neurology, Washington University, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University Medical Center, St. Louis, MO 63110, USA. Hope Center for Neurological Disorders, Washington University, St. Louis, MO 63110, USA.
10
Department of Neurology, Washington University, St. Louis, MO 63110, USA. Knight Alzheimer's Disease Research Center, Washington University Medical Center, St. Louis, MO 63110, USA.
11
Avid Radiopharmaceuticals and Eli Lilly Inc., Philadelphia, PA 19104, USA.

Abstract

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, decreased Aβ 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 Aβ production and Aβ concentrations in cerebrospinal fluid (CSF) were measured prospectively using stable isotope labeling kinetics, 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.

PMID:
24828079
PMCID:
PMC4269372
DOI:
10.1126/scitranslmed.3008169
[Indexed for MEDLINE]
Free PMC Article

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