Alzheimer’s Disease

An Antidepressant Decreases CSF Aβ Production in Healthy Individuals and in Transgenic AD Mice

Science Translational Medicine  14 May 2014:
Vol. 6, Issue 236, pp. 236re4
DOI: 10.1126/scitranslmed.3008169

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Reducing Amyloid-β with SSRIs

Higher rates of cognitive decline have been shown in cognitively normal individuals with increased brain amyloid burden, suggesting that increased amyloid burden represents a preclinical phase of Alzheimer’s disease (AD). Increased amyloid burden can occur decades before the onset of cognitive symptoms. Working in an AD mouse model and in healthy young humans, Sheline et al. tested whether an antidepressant drug could help to lower brain amyloid burden. The drug used in this study, citalopram, belongs to the selective serotonin reuptake inhibitor (SSRI) class of antidepressant drugs. The authors selected this drug because serotonin signaling is known to suppress generation of amyloid-β (Aβ) in animal models of AD. They show that in an aged transgenic AD mouse model, citalopram decreased brain Aβ concentrations in a dose-dependent manner. Further, citalopram halted the growth of preexisting brain amyloid 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. Aβ production in CSF was slowed by 37% in the citalopram group compared to placebo, and there was a 38% decrease in total CSF Aβ concentrations. The ability to safely decrease Aβ concentrations is potentially important as a preventive strategy for AD.