Tau seeding activity in the cerebrospinal fluid of Alzheimer disease patients predicts short-term cognitive decline.

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's Research & Therapy Pub Date : 2025-07-02 DOI:10.1186/s13195-025-01792-w

Ludivine Houzé, Marc Dhenain, Suzanne Lam, Fanny Petit, Stéphane Haïk, François Mouton-Liger, Jacques Hugon, Julie Dam, Claire Paquet, Ralf Jockers, Erika Cecon

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Abstract

Background: Alzheimer disease (AD) clinical progression is highly heterogeneous, making its prediction essential for the development of effective therapies. The advancement of cognitive decline in AD is tightly linked to the spread of pathological tau protein aggregates in the brain, through tau seeding properties.

Methods: We developed a cellular biosensor to measure tau seeding activity from cerebrospinal fluid (CSF) and human brain lysates. Longitudinal analysis of cognitive function was correlated with biosensor response.

Results: Individuals with CSF exhibiting high or intermediate seeding activity experienced more rapid cognitive decline compared to those with low seeding. High tau seeding was associated with total and phosphorylated tau biomarkers in AD. The biosensor also predicts the potential of human AD brain lysates to induce tau aggregation upon experimental transmission in animal models.

Conclusions: These results suggest that seeding activity might be a relevant biomarker to forecast AD pathogenicity and clinical progression.

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阿尔茨海默病患者脑脊液中的Tau种子活性可预测短期认知能力下降。

背景：阿尔茨海默病（AD）的临床进展是高度异质性的，因此对其进行预测对于开发有效的治疗方法至关重要。AD认知能力下降的进展与病理性tau蛋白聚集体在大脑中的传播密切相关，通过tau种子特性。方法：我们开发了一种细胞生物传感器来测量脑脊液（CSF）和人脑裂解物中的tau种子活性。认知功能的纵向分析与生物传感器反应相关。结果：脑脊液显示高或中等播种活性的个体比低播种活性的个体认知能力下降更快。高tau种子与AD中总tau和磷酸化tau生物标志物相关。该生物传感器还预测了人类AD脑裂解物在动物模型实验传播中诱导tau聚集的潜力。结论：这些结果提示种子活性可能是预测AD致病性和临床进展的相关生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's Research & Therapy 医学-神经病学

CiteScore

13.10

自引率

3.30%

发文量

172

审稿时长

>12 weeks

期刊介绍： Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.