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Longitudinal trajectories of Alzheimer’s ATN biomarkers in elderly persons without dementia

Published version
Peer-reviewed

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Authors

Tan, Meng-Shan 
Ji, Xi 
Li, Jie-Qiong 
Xu, Wei 
Wang, Hui-Fu 

Abstract

Abstract: Background: Models of Alzheimer’s disease (AD) pathophysiology posit that amyloidosis [A] precedes and accelerates tau pathology [T] that leads to neurodegeneration [N]. Besides this A-T-N sequence, other biomarker sequences are possible. This current work investigates and compares the longitudinal trajectories of Alzheimer’s ATN biomarker profiles in non-demented elderly adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Methods: Based on the ATN classification system, 262 individuals were identified before dementia diagnosis and accompanied by baseline and follow-up data of ATN biomarkers (CSF Aβ42, p-tau, and FDG-PET). We recorded the conversion processes in ATN biomarkers during follow-up, then analyzed the possible longitudinal trajectories and estimated the conversion rate and temporal evolution of biomarker changes. To evaluate how biomarkers changed over time, we used linear mixed-effects models. Results: During a 6–120-month follow-up period, there were four patterns of longitudinal changes in Alzheimer’s ATN biomarker profiles, from all negative to positive through the course of the disease. The most common pattern is that A pathology biomarker first emerges. As well as the classical A-T-N sequence, other “A-first,” “T-first,” and “N-first” biomarker pathways were found. The N-A-T sequence had the fastest rate of pathological progression (mean 65.00 months), followed by A-T-N (mean 67.07 months), T-A-N (mean 68.85 months), and A-N-T sequences (mean 98.14 months). Conclusions: Our current work presents a comprehensive analysis of longitudinal trajectories of Alzheimer’s ATN biomarkers in non-demented elderly adults. Stratifying disease into subtypes depending on the temporal evolution of biomarkers will benefit the early recognition and treatment.

Description

Funder: ZHANGJIANG LAB, Tianqiao and Chrissy Chen Institute, and the State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University

Keywords

Research, Alzheimer’s disease, ADNI, Amyloid, Biomarker, Tau, Neurodegeneration

Journal Title

Alzheimer's Research & Therapy

Conference Name

Journal ISSN

1758-9193

Volume Title

12

Publisher

BioMed Central
Sponsorship
National Natural Science Foundation of China (91849126, 81571245, 81501103)
National Key R&D Program of China (2018YFC1314700)
Taishan Scholars Program of Shandong Province (tsqn20161078)
Shanghai Municipal Science and Technology Major Project (No.2018SHZDZX01)