Plasma N-terminal tau fragment is an amyloid-dependent biomarker in Alzheimer's disease

IF 12.8 1区 医学 Q1 CLINICAL NEUROLOGY Alzheimer's & Dementia Pub Date : 2025-03-05 Epub Date: 2025-01-17 DOI:10.1002/alz.14550
Guoyu Lan, Laihong Zhang, Anqi Li, Wenqing Ran, Jieqin Lv, Fernando Gonzalez-Ortiz, Yue Cai, Pan Sun, Lin Liu, Jie Yang, Zhengbo He, Lili Fang, Xin Zhou, Yalin Zhu, Zhen Liu, Xuhui Chen, Xiang Fan, Dai Shi, Chenghui Ye, Linsen Xu, Qingyong Wang, Kaj Blennow, Guanxun Cheng, for the Alzheimer's Disease Neuroimaging Initiative, Pengcheng Ran, Lu Wang, Tengfei Guo
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Abstract

INTRODUCTION

Novel fluid biomarkers for tracking neurodegeneration specific to Alzheimer's disease (AD) are greatly needed.

METHODS

Using two independent well-characterized cohorts (n = 881 in total), we investigated the group differences in plasma N-terminal tau (NT1-tau) fragments across different AD stages and their association with cross-sectional and longitudinal amyloid beta (Aβ) plaques, tau tangles, brain atrophy, and cognitive decline.

RESULTS

Plasma NT1-tau significantly increased in symptomatic AD and displayed positive associations with Aβ PET (positron emission tomography) and tau PET. Higher baseline NT1-tau levels predicted greater tau PET, with 2- to 10-year intervals and faster longitudinal Aβ PET increases, AD-typical neurodegeneration, and cognitive decline. Plasma NT1-tau showed negative correlations with baseline regional brain volume and thickness, superior to plasma brain-derived tau (BD-tau) and neurofilament light (NfL) in Aβ-positive participants.

DISCUSSION

This study suggests that plasma NT1-tau is an Aβ-dependent biomarker and outperforms BD-tau and NfL in detecting cross-sectional neurodegeneration in the AD continuum.

Highlights

  • Plasma N-terminal tau (NT1-tau) was specifically increased in the A+/T+ stage.
  • Plasma NT1-tau was positively associated with greater amyloid beta (Aβ) and tau PET (positron emission tomography) accumulations.
  • Higher plasma NT1-tau predicted greater tau burden and faster Aβ increases.
  • Plasma NT1-tau was more related to neurodegeneration than plasma brain-derived tau (BD-tau) and neurofilament light (NfL).

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血浆n端tau片段是阿尔茨海默病中淀粉样蛋白依赖的生物标志物
迫切需要新的液体生物标志物来跟踪阿尔茨海默病(AD)特异性的神经退行性变。
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来源期刊
Alzheimer's & Dementia
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.
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