Peripheral Transport Proteins Were Associated with 4-Year Cognitive Decline in APOE ε4 Non-Carriers: A Longitudinal, Population-Based Study

Background: Soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) play major roles in peripheral clearance of amyloid-beta (A beta). Objective: To determine the relationship between baseline sLRP1/sRAGE and early cognitive decline in a longitudinal study and explore the possible effect of apolipoprotein E (APOE) on their association. Methods: Cognitively normal subjects were followed-up for 4 years. The baseline plasma levels of sLRP1 and sRAGE were measured using commercial ELISA kits. Global cognition was evaluated by Mini-Mental State Examination (MMSE), and cognitive decline was defined as a >= 2-point decrease of MMSE after 4 years. The association between baseline sLRP1/sRAGE and 4-year cognitive decline were analyzed using logistic regression analysis. Interaction analysis was performed to discover the potential effect of APOE genotype on the relationship. Results: 769 participants were included in the final analysis, with 122 subjects (15.86%) were cognitive decline. Baseline sLRP1/sRAGE levels were not associated with 4-year cognitive decline after multivariable adjustments in the total cohort. However, there was significant interaction effect between sRAGE and APOE genotype on cognitive decline (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]: 1.13-3.86,p = 0.019). Lower levels of sRAGE were associated with increased risk of cognitive decline among APOE epsilon 4 non-carriers (adjusted OR =1.60, 95% CI: 1.04-2.48, p = 0.034). Conclusion: Individuals with lower levels of sRAGE had an increased risk of 4-year cognitive decline in APOE epsilon 4 noncarriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.

Automated summary

This study aimed to explore the relationship between baseline levels of soluble low-density lipoprotein receptor-related protein-1 (sLRP1) and soluble receptor of advanced glycation end products (sRAGE) and early cognitive decline, as well as the potential influence of apolipoprotein E (APOE) genotype. The results showed that baseline levels of sLRP1 and sRAGE were not associated with 4-year cognitive decline in the total cohort. However, there was a significant interaction effect between sRAGE and APOE genotype, with lower levels of sRAGE being associated with increased risk of cognitive decline in APOE epsilon 4 non-carriers.