Apolipoprotein E epsilon 4 Allele is Associated With Plasma Amyloid Beta and Amyloid Beta Transporter Levels: A Cross-sectional Study in a Rural Area of Xi'an, China

摘要

Objective: The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (A beta) and A beta transporter levels are still unclear. Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) are the major transporter for A beta, which can prevent plasma A beta from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma A beta, sLRP1, sRAGE levels. Design: Cross-sectional study. Setting: The committee office of the village. Participants: Residents lived in the village for more than 3 years, aged 40-85 years (n = 1,119, 63.5% women). Measurements: Plasma biomarkers include ApoE genotype, A beta, sLRP1, sRAGE, fasting blood-glucose, and blood lipids. General information, medical history, living habits, and cognitive status (cognitive impairment or not) were also collected. Results: After controlling for all possible covariates, multiple linear regression analysis showed that the plasma level of A beta(42) was higher and log-transformed sLRP1 was lower in ApoE epsilon 4 carriers than that in noncarriers (beta(A beta 42) = 1.214, 95% confidence interval: 0.105-2.316, p(A beta 42) = 0.031; beta(sLRP1) = -0.075, 95% confidence interval: -0.129 to -0.021, p(sLRP1) = 0.006, respectively). Partial correlation analysis showed that plasma A beta(40) was positively correlated with log-transformed sLRP1 and log-transformed sRAGE (r(sLRP1) = 0.116, p(sLRP1) < 0.001; r(sRAGE) = 0.078, p(sLRP1) = 0.009, respectively). Plasma A beta(42) was positively correlated with log-transformed sRAGE (r = 0.072, p = 0.017). Conclusion: ApoE epsilon 4 carriers had higher plasma A beta(42) levels and lower sLRP1 levels. These data indicated that the ApoE epsilon 4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral A beta(42) and sLRP1 levels, but it needs to be further elucidated.