Association Between Plasma Apolipoprotein M With Alzheimer's Disease: A Cross-Sectional Pilot Study From China

Jia-Yan Xin; Xiao Huang; Ying Sun; Hai-Song Jiang; Jin Fan; Neng-Wei Yu; Fu-Qiang Guo; Fang Ye; Jun Xiao; Wei-Dong Le; Shao-Jie Yang; Yang Xiang

doi:10.3389/fnagi.2022.838223

Association Between Plasma Apolipoprotein M With Alzheimer's Disease: A Cross-Sectional Pilot Study From China

Front Aging Neurosci. 2022 Mar 18:14:838223. doi: 10.3389/fnagi.2022.838223. eCollection 2022.

Authors

Jia-Yan Xin^{1

2}, Xiao Huang^{1

2}, Ying Sun³, Hai-Song Jiang⁴, Jin Fan², Neng-Wei Yu⁵, Fu-Qiang Guo⁵, Fang Ye⁵, Jun Xiao⁵, Wei-Dong Le⁴, Shao-Jie Yang⁶, Yang Xiang⁵

Affiliations

¹ Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China.
² Department of Neurology, General Hospital of Western Theater Command, Chengdu, China.
³ Department of Geriatrics, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁴ Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China.
⁵ Department of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
⁶ Department of Neurology, Chengdu Eighth People's Hospital, Chengdu, China.

Abstract

Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD.

Methods: A multicenter, cross-sectional study recruited patients with AD (n = 67), age- and sex-matched cognitively normal (CN) controls (n = 73). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, we examined and compared the plasma levels of ApoM, tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL). Multivariate logistic regression analysis was applied to determine the association of plasma ApoM with the presence of AD. The correlation analysis was used to explore the correlations between plasma ApoM with cognitive function [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)], activities of daily living (ADL), and the representative blood-based biomarkers (plasma p-tau217 and NfL). Receiver operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma ApoM.

Results: Plasma ApoM and its derived indicators (ratios of ApoM/TC, ApoM/TG, ApoM/HDL-C, and ApoM/LDL-C) were significantly higher in AD group than those in CN group (each p < 0.0001). After adjusted for the risk factors of AD, the plasma ApoM and its derived indicators were significantly associated with the presence of AD, respectively. ApoM (OR = 1.058, 95% CI: 1.027-1.090, p < 0.0001), ApoM/TC ratio (OR = 1.239, 95% CI: 1.120-1.372, p < 0.0001), ApoM/TG ratio (OR = 1.064, 95% CI: 1.035-1.095, p < 0.0001), ApoM/HDL-C ratio (OR = 1.069, 95% CI: 1.037-1.102, p < 0.0001), and ApoM/LDL-C ratio (OR = 1.064, 95% CI:1.023-1.106, p = 0.002). In total participants, plasma ApoM was significantly positively correlated with plasma p-tau217, plasma NfL, and ADL (each p < 0.0001) and significantly negatively correlated with MMSE and MoCA (each p < 0.0001), respectively. In further subgroup analyses, these associations remained in different APOEϵ 4 status participants and sex subgroups. ApoM/TC ratio (ΔAUC = 0.056, p = 0.044) and ApoM/TG ratio (ΔAUC = 0.097, p = 0.011) had a statistically remarkably larger AUC than ApoM, respectively. The independent addition of ApoM and its derived indicators to the basic model [combining age, sex, APOEϵ 4, and body mass index (BMI)] led to the significant improvement in diagnostic power, respectively (each p < 0.05).

Conclusion: All the findings preliminarily uncovered the association between plasma ApoM and AD and provided more evidence of the potential of ApoM as a candidate biomarker of AD.

Keywords: Alzheimer’s disease; apolipoprotein M; biomarker; neurofilament light chain; tau.