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

被引:27
作者
Tan, Meng-Shan [1 ]
Ji, Xi [2 ]
Li, Jie-Qiong [1 ]
Xu, Wei [1 ]
Wang, Hui-Fu [1 ]
Tan, Chen-Chen [1 ]
Dong, Qiang [3 ,4 ]
Zuo, Chuan-Tao [5 ]
Tan, Lan [1 ,2 ]
Suckling, John [6 ,7 ,8 ,9 ]
Yu, Jin-Tai [3 ,4 ]
机构
[1] Qingdao Univ, Qingdao Municipal Hosp, Dept Neurol, Qingdao, Peoples R China
[2] Dalian Med Univ, Dept Neurol, Dalian, Peoples R China
[3] Fudan Univ, Huashan Hosp, Shanghai Med Coll, Dept Neurol, 12th Wulumuqi Zhong Rd, Shanghai 200040, Peoples R China
[4] Fudan Univ, Huashan Hosp, Shanghai Med Coll, Inst Neurol, 12th Wulumuqi Zhong Rd, Shanghai 200040, Peoples R China
[5] Fudan Univ, Huashan Hosp, PET Ctr, Shanghai, Peoples R China
[6] Univ Cambridge, Dept Psychiat, Cambridge, England
[7] Univ Cambridge, Med Res Council, Cambridge, England
[8] Univ Cambridge, Wellcome Trust Behav & Clin Neurosci Inst, Cambridge, England
[9] Cambridgeshire & Peterborough NHS Trust, Cambridge, England
基金
中国国家自然科学基金; 国家重点研发计划;
关键词
Alzheimer's disease; ADNI; Amyloid; Biomarker; Tau; Neurodegeneration; ASSOCIATION WORKGROUPS; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; DISEASE; BETA; TAU; RECOMMENDATIONS; NEURODEGENERATION; INDIVIDUALS; TRACKING;
D O I
10.1186/s13195-020-00621-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 A beta 42, 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.
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页数:7
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