The level of plasma amyloid-β 40 is correlated with peripheral transport proteins in cognitively normal adults: A population-based cross-sectional study

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 Aβ 40, Aβ 42, 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 Aβ 40 (r= 0.103, p < 0.001; r= 0.064, p = 0.027, respectively), but neither were associated with plasma Aβ 42. After multivariable adjustment in the regression model, Log sLRP1 and Log sRAGE were still positively related with plasma Aβ 40 (β= 2.969, p < 0.001; β= 1.936, p = 0.017, respectively) but not Aβ 42. Furthermore, the positive correlations between transport proteins and plasma Aβ 40 remained significant only in APOE ϵ4 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 Aβ 40 in cognitively normal adults, especially in APOE ϵ4 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.