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

Alzheimer’s Research & Therapy

Alzheimer’s Disease Neuroimaging Initiative¹  Qiang Dong²  Jin-Tai Yu²  Xi Ji³  Hui-Fu Wang⁴  Wei Xu⁴  Lan Tan⁴  Chen-Chen Tan⁴  Meng-Shan Tan⁴  Jie-Qiong Li⁴  John Suckling⁵  Chuan-Tao Zuo⁶ 

[1] ;Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University;Department of Neurology, Dalian Medical University;Department of Neurology, Qingdao Municipal Hospital, Qingdao University;Department of Psychiatry, University of Cambridge;PET Center, Huashan Hospital, Fudan University;

关键词: Alzheimer’s disease;    ADNI;    Amyloid;    Biomarker;    Tau;    Neurodegeneration;   

DOI  :  10.1186/s13195-020-00621-6

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown