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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This post is Copyright: 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 | January 17, 2025