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

• Published in: Translational psychiatry Vol. 11; no. 1; pp. 356 - 10
• Main Authors: Chen, Shi-Dong, Huang, Yu-Yuan, Shen, Xue-Ning, Guo, Yu, Tan, Lan, Dong, Qiang, Yu, Jin-Tai
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.06.2021; Nature Publishing Group
• Subjects: 631/378; 692/53; Alzheimer's disease; Behavioral Sciences; Biological Psychology; Biomarkers; Cognition & reasoning; Dementia; Medicine; Medicine & Public Health; Neurosciences; Pharmacotherapy; Plasma; Psychiatry
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-021-01476-7

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 (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stage of AD. A longitudinal increase of plasma p-tau181 was associated with abnormal cerebrospinal fluid biomarker levels (low Aβ42, 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 Aβ-positive group and became non-significant in Aβ-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.