INTRODUCTIONNovel fluid biomarkers for tracking neurodegeneration specific to Alzheimer's disease (AD) are greatly needed. METHODSUsing 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 (A beta) plaques, tau tangles, brain atrophy, and cognitive decline. RESULTSPlasma NT1-tau significantly increased in symptomatic AD and displayed positive associations with A beta 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 A beta 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 A beta-positive participants. DISCUSSIONThis study suggests that plasma NT1-tau is an A beta-dependent biomarker and outperforms BD-tau and NfL in detecting cross-sectional neurodegeneration in the AD continuum.
基金：
National Natural Science Foundation of China [U01 AG024904]; ADNI (National Institutes of Health) [W81XWH-12-2-0012]; DOD ADNI (Department of Defense); National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; Biogen; CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; Fujirebio; Johnson & Johnson Pharmaceutical Research & Development LLC.; Meso Scale Diagnostics; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Takeda Pharmaceutical Company; Canadian Institutes of Health Research; ADNI clinical sites in Canada; Foundation for the National Institutes of Health; Northern California Institute for Research and Education [82171197, 82301380]; Laboratory for Neuro Imaging at the University of Southern California - National Natural Science Foundation of China [2023B1515020113]; Guangdong Basic and Applied Basic Science Foundation for Distinguished Young Scholars [RCYX20221008092935096]; Shenzhen Science and Technology Program [2023YFC3605400]; National Key Research and Development Program of China; Shenzhen Bay Laboratory [LG-GG-202401-ADA070600]; Lingang Laboratory
第一作者机构：[1]Shenzhen Bay Lab, Inst Neurol & Psychiat Disorders, 5 Kelian Rd, Shenzhen 518132, Peoples R China
通讯作者：
通讯机构：[1]Shenzhen Bay Lab, Inst Neurol & Psychiat Disorders, 5 Kelian Rd, Shenzhen 518132, Peoples R China[18]Shenzhen Bay Lab, Inst Biomed Engn, Shenzhen, Peoples R China[19]Peking Univ, Shenzhen Grad Sch, Shenzhen, Peoples R China
推荐引用方式(GB/T 7714)：
Lan Guoyu,Zhang Laihong,Li Anqi,et al.Plasma N-terminal tau fragment is an amyloid-dependent biomarker in Alzheimer's disease[J].ALZHEIMERS & DEMENTIA.2025,doi:10.1002/alz.14550.
APA：
Lan, Guoyu,Zhang, Laihong,Li, Anqi,Ran, Wenqing,Lv, Jieqin...&Guo, Tengfei.(2025).Plasma N-terminal tau fragment is an amyloid-dependent biomarker in Alzheimer's disease.ALZHEIMERS & DEMENTIA,,
MLA：
Lan, Guoyu,et al."Plasma N-terminal tau fragment is an amyloid-dependent biomarker in Alzheimer's disease".ALZHEIMERS & DEMENTIA .(2025)
医学