Longitudinal plasma phosphorylated tau 181 tracks disease progression in Alzheimer's disease

被引:39
作者
Chen, Shi-Dong [1 ,2 ]
Huang, Yu-Yuan [1 ,2 ]
Shen, Xue-Ning [1 ,2 ]
Guo, Yu [3 ]
Tan, Lan [3 ]
Dong, Qiang [1 ,2 ]
Yu, Jin-Tai [1 ,2 ]
机构
[1] Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Neurol, Shanghai, Peoples R China
[2] Fudan Univ, Huashan Hosp, Shanghai Med Coll, Inst Neurol, Shanghai, Peoples R China
[3] Qingdao Univ, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
NEUROIMAGING INITIATIVE ADNI; SERUM NEUROFILAMENT LIGHT; COMPOSITE SCORE; BIOMARKER; DEFINITION; PROTEIN; BLOOD;
D O I
10.1038/s41398-021-01476-7
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
To assess plasma phosphorylated tau181 (p-tau181) as a progression biomarker in Alzheimer's disease (AD), we examined longitudinal plasma p-tau181 of 1184 participants (403 cognitively normal (CN), 560 patients with mild cognitive impairment (MCI), and 221 with AD dementia) from Alzheimer's Disease Neuroimaging Initiative (ADNI). The plasma p-tau level was increased at baseline for MCI and AD dementia (mean: CN, 15.4 pg/mL; MCI, 18.4 pg/mL; AD dementia, 23.7 pg/mL; P < 0.001) and increased significantly over time at preclinical (A beta-positive CN), prodromal (A beta-positive MCI), and dementia (A beta-positive dementia) stage of AD. A longitudinal increase of plasma p-tau181 was associated with abnormal cerebrospinal fluid biomarker levels (low A beta 42, high phosphorylated tau, and high total tau, all P < 0.001), amyloid accumulation (P < 0.001) and hypometabolism (P = 0.002) on positron emission tomography, atrophy in structure imaging (small hippocampal (P = 0.030), middle temporal (P = 0.008), and whole brain (P = 0.027) volume, and large ventricular volume (P = 0.008)), and deteriorated cognitive performance (global cognition and memory, language, executive function, and visuospatial function, all P < 0.050) at baseline. Furthermore, longitudinal plasma p-tau181 correlated with concurrent changes of nearly all these AD-related hallmarks and faster increase in plasma p-tau181 correlated with faster worsening cognition in all diagnostic groups. Importantly, most associations remained significant in A beta-positive group and became non-significant in A beta-negative group. Longitudinal analyses of plasma p-tau181 suggest its potential as a noninvasive biomarker to track disease progression in AD and to monitor effects of disease-modifying therapeutics in clinical trials.
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页数:10
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