Dylan J. Terstege, Shaista Jabeen, Alzheimer's Disease Neuroimaging Initiative, Liisa A. M. Galea, Jonathan R. Epp, Derya Sargin
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As a serotonergic hub, DRN activity is altered by selective serotonin reuptake inhibitors (SSRIs), which also have variable effects on cognitive decline and pathology in AD.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We examined <i>N </i>= 191 subjects with baseline <sup>18</sup>F-fluorodeoxyglucose positron emission tomography and plasma biomarker data to study the effects of SSRIs on tau pathology, cognitive decline, and DRN metabolism.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Plasma phosphorylated tau 181 (p-tau181) was lower with SSRI use. The effect of SSRIs on cognition varied by cognitive assessment. The DRN was hypometabolic in AD patients relative to healthy controls; however, SSRI use restored the metabolic activity of this region in AD patients.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>Long-term SSRI use may reduce the pathological presentation of AD but has variable effects on cognitive performance.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Tau pathology spreads throughout the brain during AD pathogenesis.</li>\n \n <li>The DRN is among the first regions to develop tau pathology during this process.</li>\n \n <li>SSRI use restores the metabolic activity of the DRN and reduces plasma p-tau181.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 2","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14579","citationCount":"0","resultStr":"{\"title\":\"SSRIs reduce plasma tau and restore dorsal raphe metabolism in Alzheimer's disease\",\"authors\":\"Dylan J. Terstege, Shaista Jabeen, Alzheimer's Disease Neuroimaging Initiative, Liisa A. M. Galea, Jonathan R. Epp, Derya Sargin\",\"doi\":\"10.1002/alz.14579\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Tau pathology impacts neurodegeneration and cognitive decline in Alzheimer's disease (AD), with the dorsal raphe nucleus (DRN) being among the brain regions showing the earliest tau pathology. 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SSRIs reduce plasma tau and restore dorsal raphe metabolism in Alzheimer's disease
INTRODUCTION
Tau pathology impacts neurodegeneration and cognitive decline in Alzheimer's disease (AD), with the dorsal raphe nucleus (DRN) being among the brain regions showing the earliest tau pathology. As a serotonergic hub, DRN activity is altered by selective serotonin reuptake inhibitors (SSRIs), which also have variable effects on cognitive decline and pathology in AD.
METHODS
We examined N = 191 subjects with baseline 18F-fluorodeoxyglucose positron emission tomography and plasma biomarker data to study the effects of SSRIs on tau pathology, cognitive decline, and DRN metabolism.
RESULTS
Plasma phosphorylated tau 181 (p-tau181) was lower with SSRI use. The effect of SSRIs on cognition varied by cognitive assessment. The DRN was hypometabolic in AD patients relative to healthy controls; however, SSRI use restored the metabolic activity of this region in AD patients.
DISCUSSION
Long-term SSRI use may reduce the pathological presentation of AD but has variable effects on cognitive performance.
Highlights
Tau pathology spreads throughout the brain during AD pathogenesis.
The DRN is among the first regions to develop tau pathology during this process.
SSRI use restores the metabolic activity of the DRN and reduces plasma p-tau181.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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