Apolipoprotein E ε4 Allele is Associated With Plasma Amyloid Beta and Amyloid Beta Transporter Levels: A Cross-sectional Study in a Rural Area of Xi'an, China

Objective: The effects of the Apolipoprotein E (ApoE) genotype on peripheral amyloid beta (Aβ) and Aβ 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 Aβ, which can prevent plasma Aβ from flowing into brain. The aim of this study was to investigate the relationships between the ApoE genotype and plasma Aβ, 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, Aβ, 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 Aβ₄₂ was higher and log-transformed sLRP1 was lower in ApoE ε4 carriers than that in noncarriers (β_Aβ42 = 1.214, 95% confidence interval: 0.105–2.316, p_Aβ42 = 0.031; β_sLRP1 = −0.075, 95% confidence interval: −0.129 to −0.021, p_sLRP1 = 0.006, respectively). Partial correlation analysis showed that plasma Aβ₄₀ 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 Aβ₄₂ was positively correlated with log-transformed sRAGE (r = 0.072, p = 0.017). Conclusion: ApoE ε4 carriers had higher plasma Aβ₄₂ levels and lower sLRP1 levels. These data indicated that the ApoE ε4 allele may also contribute to the pathogenesis of Alzheimer's disease through its effects on peripheral Aβ₄₂ and sLRP1 levels, but it needs to be further elucidated.