The Level of Plasma Amyloid-β₄₀ Is Correlated with Peripheral Transport Proteins in Cognitively Normal Adults: A Population-Based Cross-Sectional Study

Article type: Research Article

Authors: Gao, Ling^{a; 1} | Jiang, Yu^{a; 1} | Wei, Shan^a | Shang, Suhang^a | Li, Pei^a | Chen, Chen^a | Dang, Liangjun^a | Wang, Jin^a | Huo, Kang^a | Deng, Meiying^a | Wang, Jingyi^b | Zhang, Rong^c | Qu, Qiumin^{a; *}

Affiliations: [a] Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China | [b] Huxian Hospital of Traditional Chinese Medicine, Xi’an, China | [c] Cerebrovascular Laboratory, Institute for Exercise and Environmental Medicine, UT Southwestern Medical Center at Dallas, Dallas, TX, USA

Correspondence: [*] Correspondence to: Qiumin Qu, Department of Neurology, The First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Rd, Xi’an 710061, China. Tel./Fax: +86 29 8532 4083; Email: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background:Transport proteins, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), and soluble receptor of advanced glycation end products (sRAGE), play an important role in the clearance of plasma amyloid-β (Aβ). However, their relationship is not clear. Objective:The aim was to explore the relationship between plasma levels of sLRP1, sRAGE, and Aβ in a cross-sectional study. Methods:A total of 1,185 cognitively normal participants (age above 40) from a village in the suburbs of Xi’an, China were enrolled from October 8, 2014 to March 30, 2015. Plasma Aβ40, Aβ42, sLRP1, and sRAGE were tested using a commercial ELISA. Apolipoprotein E (APOE) genotyping was conducted using PCR and sequencing. The relationship between plasma levels of sLRP1, sRAGE, and Aβ was analyzed using Pearson’s correlation analysis and multiple linear regression. Results:In the total population, Log sLRP1 and Log sRAGE were positively correlated with plasma Aβ40 (r= 0.103, p < 0.001; r= 0.064, p = 0.027, respectively), but neither were associated with plasma Aβ42. After multivariable adjustment in the regression model, Log sLRP1 and Log sRAGE were still positively related with plasma Aβ40 (β= 2.969, p < 0.001; β= 1.936, p = 0.017, respectively) but not Aβ42. Furthermore, the positive correlations between transport proteins and plasma Aβ40 remained significant only in APOE ɛ4 non-carriers after Pearson’s analysis and multiple regression analysis after stratification by gene status. Conclusion:The concentrations of plasma sLRP1 and sRAGE had a significant impact on the level of plasma Aβ40 in cognitively normal adults, especially in APOE ɛ4 non-carriers. However, the mechanism by which the transport proteins are involved in peripheral Aβ clearance and the relationship between transporters and amyloid burden in the brain needs further validation.

Keywords: Alzheimer’s disease, amyloid-β, soluble low-density lipoprotein receptor-related protein-1 (sLRP1), soluble receptor of advanced glycation end products (sRAGE), transport proteins

DOI: 10.3233/JAD-180399

Journal: Journal of Alzheimer's Disease, vol. 65, no. 3, pp. 951-961, 2018