Head-to-head comparison of plasma and PET imaging ATN markers in subjects with cognitive complaints
Jiaying Lu, Xiaoxi Ma, Huiwei Zhang, Zhenxu Xiao, Ming Li, Jie Wu, Zizhao Ju, Li Chen, Li Zheng, Jingjie Ge, Xiaoniu Liang, Weiqi Bao, Ping Wu, Ding Ding, Tzu‐Chen Yen, Yihui Guan, Chuantao Zuo, Qianhua Zhao, on behalf of the Shanghai Memory Study (SMS), Keliang Chen, Langfeng Shi, Wanqing Wu, Yan Zhou, Yan Zhang, Fang Pei
Abstract
Abstract Background Gaining more information about the reciprocal associations between different biomarkers within the ATN (Amyloid/Tau/Neurodegeneration) framework across the Alzheimer’s disease (AD) spectrum is clinically relevant. We aimed to conduct a comprehensive head-to-head comparison of plasma and positron emission tomography (PET) ATN biomarkers in subjects with cognitive complaints. Methods A hospital-based cohort of subjects with cognitive complaints with a concurrent blood draw and ATN PET imaging ( 18 F-florbetapir for A, 18 F-Florzolotau for T, and 18 F-fluorodeoxyglucose [ 18 F-FDG] for N) was enrolled ( n = 137). The β-amyloid (Aβ) status (positive versus negative) and the severity of cognitive impairment served as the main outcome measures for assessing biomarker performances. Results Plasma phosphorylated tau 181 (p-tau181) level was found to be associated with PET imaging of ATN biomarkers in the entire cohort. Plasma p-tau181 level and PET standardized uptake value ratios of AT biomarkers showed a similarly excellent diagnostic performance for distinguishing between Aβ+ and Aβ− subjects. An increased tau burden and glucose hypometabolism were significantly associated with the severity of cognitive impairment in Aβ+ subjects. Additionally, glucose hypometabolism – along with elevated plasma neurofilament light chain level – was related to more severe cognitive impairment in Aβ− subjects. Conclusion Plasma p-tau181, as well as 18 F-florbetapir and 18 F-Florzolotau PET imaging can be considered as interchangeable biomarkers in the assessment of Aβ status in symptomatic stages of AD. 18 F-Florzolotau and 18 F-FDG PET imaging could serve as biomarkers for the severity of cognitive impairment. Our findings have implications for establishing a roadmap to identifying the most suitable ATN biomarkers for clinical use.