Plasma Aβ42/Aβ40 and p-tau181 Predict Long-Term Clinical Progression in a Cohort with Amnestic Mild Cognitive Impairment

Author:

Xiao Zhenxu123,Wu Wanqing123,Ma Xiaoxi123,Liang Xiaoniu123,Lu Jiaying4,Zheng Li123,Ding Saineng123,Lei Qiqi5,Luo Jianfeng5,Chen Keliang123,Ding Ding123,Zhao Qianhua1236

Affiliation:

1. Institute of Neurology, Huashan Hospital, Fudan University , Shanghai , China

2. National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University , Shanghai , China

3. National Center for Neurological Disorders, Huashan Hospital, Fudan University , Shanghai , China

4. PET Center, Huashan Hospital, Fudan University , Shanghai , China

5. Department of Biostatistics, School of Public Health, Fudan University , Shanghai , China

6. MOE Frontiers Center for Brain Science, Fudan University , Shanghai , China

Abstract

Abstract Background Previous studies reported the value of blood-based biomarkers in predicting Alzheimer disease (AD) progression among individuals with different disease stages. However, evidence regarding the value of these markers in those with amnestic mild cognitive impairment (aMCI) is insufficient. Methods A cohort with 251 aMCI individuals were followed for up to 8 years. Baseline blood biomarkers were measured on a single-molecule array platform. Multipoint clinical diagnosis and domain-specific cognitive functions were assessed to investigate the longitudinal relationship between blood biomarkers and clinical AD progression. Results Individuals with low Aβ42/Aβ40 and high p-tau181 at baseline demonstrated the highest AD risk (hazard ratio = 4.83, 95% CI 2.37–9.86), and the most dramatic decline across cognitive domains. Aβ42/Aβ40 and p-tau181, combined with basic characteristics performed the best in predicting AD conversion (AUC = 0.825, 95% CI 0.771–0.878). Conclusions Combining Aβ42/Aβ40 and p-tau181 may be a feasible indicator for AD progression in clinical practice, and a potential composite marker in clinical trials.

Funder

Shanghai Hospital Development Center

National Natural Science Foundation of China

MOE Frontiers Center for Brain Science

Shanghai Municipal Science and Technology Major Project

ZJ LAB, National Natural Science Foundation of China

Key Project of the Ministry of Science and Technology, China

National Project of Chronic Disease

Scientific Research Plan Project of Shanghai Science and Technology Committee

Publisher

Oxford University Press (OUP)

Subject

Biochemistry (medical),Clinical Biochemistry

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