SSRIs reduce plasma tau and restore dorsal raphe metabolism in Alzheimer's disease

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-02-12 DOI:10.1002/alz.14579

Dylan J. Terstege, Shaista Jabeen, Alzheimer's Disease Neuroimaging Initiative, Liisa A. M. Galea, Jonathan R. Epp, Derya Sargin

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Abstract

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.

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SSRIs 可降低血浆 tau 含量并恢复阿尔茨海默氏症患者背侧大脑皮质的新陈代谢

Tau病理影响阿尔茨海默病（AD）的神经退行性变和认知能力下降，中隔背核（DRN）是最早显示Tau病理的大脑区域之一。作为5 -羟色胺能中枢，DRN活性可被选择性5 -羟色胺再摄取抑制剂（SSRIs）改变，这对AD的认知能力下降和病理也有不同的影响。方法：我们使用基线18f -氟脱氧葡萄糖正电子发射断层扫描和血浆生物标志物数据对N = 191名受试者进行检查，研究SSRIs对tau病理、认知能力下降和DRN代谢的影响。结果血浆磷酸化tau181 （p-tau181）随SSRI的使用而降低。SSRIs对认知的影响因认知评估而异。与健康对照组相比，AD患者的DRN代谢水平较低；然而，使用SSRI可以恢复AD患者该区域的代谢活性。长期使用SSRI可以减少AD的病理表现，但对认知表现有不同的影响。在阿尔茨海默病发病过程中，Tau蛋白病理扩散到整个大脑。DRN是在这一过程中首先出现tau病理的区域之一。使用SSRI可恢复DRN的代谢活性并降低血浆p-tau181。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

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.