The relationship of soluble tau species with Alzheimer's disease amyloid plaque removal and tau pathology

IF 11.1 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-09-23 DOI:10.1002/alz.70689

Eric M. McDade, Nicolas R. Barthélemy, Guoqiao Wang, Yan Li, Yuchen Cao, Brian Gordon, Tammie L. S. Benzinger, David Clifford, Alison M. Goate, Alan E. Renton, Jason Hassenstab, Jorge J. Llibre-Guerra, Richard J. Perrin, Chengjie Xiong, Carlos Cruchaga, Catherine J. Mummery, Sarah B. Berman, James Lah, Erik D. Roberson, Christopher Van Dyck, Serge Gauthier, Colin L. Masters, Mario Masellis, Tobias Bittner, Roy Yaari, Jasmeer Chhatwal, Patricio Chrem, William Brooks, Kazushi Suzuki, Johannes J. Levin, Mathias Jucker, John Ringman, David Wallon, Takeshi Ikeuchi, Jae-Hong Lee, Jee Hoon Roh, Peter Schofield, Nick C. Fox, Natalie S. Ryan, Jonathan Vöglein, Celeste Karch, Laura Ibáñez, Gregory S. Day, Raquel Sánchez-Valle, Alisha Daniels, John C. Morris, Charlene Supnet-Bell, Allan I. Levey, Randall J. Bateman, The DIAN-TU Study Team and DIAN Obs Team

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引用次数: 0

Abstract

BACKGROUND

Tau-derived cerebrospinal fluid (CSF) biomarkers correlate with amyloid-beta (Aβ) plaques or tau tangles in Alzheimer's disease (AD). This study assessed the effects of long-term anti-Aβ antibodies on amyloid plaques, tau tangles, and CSF tau species to determine the relationships between them.

METHODS

A post-hoc analysis of the DIAN-TU-001 trial (NCT01760005) examined 142 participants at risk for dominantly inherited AD randomized to solanezumab (n = 50), gantenerumab (n = 52), or placebo (n = 40). High-resolution mass spectrometry quantified CSF tau species over four years.

RESULTS

Phosphorylated tau (p-tau) species (153, 181, 217, 231) increased early in preclinical AD but were reduced with gantenerumab-mediated Aβ plaque reduction. Nearly a decade later, MTBR-tau243 and p-tau205 increased, showing no association with Aβ reduction, aligning with tau tangle pathology progression.

DISCUSSION

Initially changing soluble p-tau species track Aβ plaque reduction, while ptau205 and MTBR-243 reflect tau tangle pathology, informing different pathways of therapeutic strategies.

Highlights

p-tau217 and p-tau231 correlate with Aβ-PET and respond to Aβ-plaque lowering therapies.
Aβ immunotherapy trials support a direct link between p-tau changes and Aβ plaques
Gantenerumab reduces Aβ plaques but does not affect tau NFT-related biomarkers.
Blood-based p-tau217 assays may provide a non-invasive tool to monitor Aβ therapies.
MTBR-tau243 strongly correlates with tau PET and tracks NFT pathology progression.
Further studies are needed to validate tau biomarkers for tracking NFT-targeting therapies.

Abstract Image

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可溶性tau蛋白与阿尔茨海默病淀粉样斑块去除和tau蛋白病理的关系

tau来源的脑脊液（CSF）生物标志物与阿尔茨海默病（AD）的淀粉样蛋白斑块或tau缠结相关。本研究评估了长期抗a β抗体对淀粉样斑块、tau缠结和CSF tau物种的影响，以确定它们之间的关系。

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 & 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.