首都医科大学宣武医院贾建平团队研究了阿尔茨海默病确诊前20年的生物标志物变化。2024年2月21日出版的《新英格兰医学杂志》发表了这项成果。

在纵向研究中，从正常认知到诊断散发性阿尔茨海默病之间发生的生物标志物变化尚未得到广泛研究。

研究组对2000年1月至2020年12月参加中国认知与衰老研究的认知正常参与者进行了一项阿尔茨海默病生物标志物的多中心嵌套病例对照研究。这些参与者的一个亚组每隔2年至3年接受一次脑脊液（CSF）测试、认知评估和大脑成像。共有648名患阿尔茨海默病的参与者与648名认知正常的参与者进行了匹配，并分析了两组患者的CSF生化标志物浓度、认知测试和成像的时间轨迹。

中位随访时间为19.9年（四分位间距19.5-20.2年）。阿尔茨海默病组的CSF和成像生物标志物在诊断前的以下估计年数与认知正常组存在差异：淀粉样蛋白β（Aβ）₄₂，18年；Aβ₄₂与Aβ₄₀之比，14年；磷酸化tau 181，11年；总tau，10年；神经丝轻链，9年；海马体积，8年；认知能力下降，6年。随着认知障碍的进展，阿尔茨海默病组CSF生物标志物水平的变化最初加速，然后减缓。

研究组表明，在这项涉及散发性阿尔茨海默病临床诊断前20年的中国参与者的研究中，研究组观察了CSF生物标志物的时间进程、诊断前它们与认知正常的匹配参与者的生物标志物偏离的时间，以及生物标志物变为异常的时间顺序。

附：英文原文

Title: Biomarker Changes during 20 Years Preceding Alzheimer’s Disease

Author: Jianping Jia, Yuye Ning, Meilin Chen, Shuheng Wang, Hao Yang, Fangyu Li, Jiayi Ding, Yan Li, Bote Zhao, Jihui Lyu, Shanshan Yang, Xin Yan, Yue Wang, Wei Qin, Qi Wang, Ying Li, Jintao Zhang, Furu Liang, Zhengluan Liao, Shan Wang

Issue&Volume: 2024-02-21

Abstract:

Background

Biomarker changes that occur in the period between normal cognition and the diagnosis of sporadic Alzheimer’s disease have not been extensively investigated in longitudinal studies.

Methods

We conducted a multicenter, nested case–control study of Alzheimer’s disease biomarkers in cognitively normal participants who were enrolled in the China Cognition and Aging Study from January 2000 through December 2020. A subgroup of these participants underwent testing of cerebrospinal fluid (CSF), cognitive assessments, and brain imaging at 2-year–to–3-year intervals. A total of 648 participants in whom Alzheimer’s disease developed were matched with 648 participants who had normal cognition, and the temporal trajectories of CSF biochemical marker concentrations, cognitive testing, and imaging were analyzed in the two groups.

Results

The median follow-up was 19.9 years (interquartile range, 19.5 to 20.2). CSF and imaging biomarkers in the Alzheimer’s disease group diverged from those in the cognitively normal group at the following estimated number of years before diagnosis: amyloid-beta (Aβ)42, 18 years; the ratio of Aβ42 to Aβ40, 14 years; phosphorylated tau 181, 11 years; total tau, 10 years; neurofilament light chain, 9 years; hippocampal volume, 8 years; and cognitive decline, 6 years. As cognitive impairment progressed, the changes in CSF biomarker levels in the Alzheimer’s disease group initially accelerated and then slowed.

Conclusions

In this study involving Chinese participants during the 20 years preceding clinical diagnosis of sporadic Alzheimer’s disease, we observed the time courses of CSF biomarkers, the times before diagnosis at which they diverged from the biomarkers from a matched group of participants who remained cognitively normal, and the temporal order in which the biomarkers became abnormal.

DOI: 10.1056/NEJMoa2310168

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2310168