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

Zhenxu Xiao; Wanqing Wu; Xiaoxi Ma; Xiaoniu Liang; Jiaying Lu; Li Zheng; Saineng Ding; Qiqi Lei; Jianfeng Luo; Keliang Chen; Ding Ding; Qianhua Zhao

doi:10.1093/clinchem/hvac149

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

Clin Chem. 2022 Dec 6;68(12):1552-1563. doi: 10.1093/clinchem/hvac149.

Authors

Zhenxu Xiao^{1

2

3}, Wanqing Wu^{1

2

3}, Xiaoxi Ma^{1

2

3}, Xiaoniu Liang^{1

2

3}, Jiaying Lu⁴, Li Zheng^{1

2

3}, Saineng Ding^{1

2

3}, Qiqi Lei⁵, Jianfeng Luo⁵, Keliang Chen^{1

2

3}, Ding Ding^{1

2

3}, Qianhua Zhao^{1

2

3

6}

Affiliations

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.

PMID: 36208187
DOI: 10.1093/clinchem/hvac149

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / diagnosis
Amyloid beta-Peptides
Biomarkers
Cognitive Dysfunction* / diagnosis
Humans
Peptide Fragments
tau Proteins

Substances

amyloid beta-protein (1-42)
Amyloid beta-Peptides
Peptide Fragments
Biomarkers
tau Proteins