Peripheral transport proteins were associated with 4‐year cognitive decline in APOE ε4 non‐carriers: A longitudinal, population‐based study

Abstract

AbstractBackgroundSoluble 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‐β (Aβ).We aim 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.MethodCognitively 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.Result769 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 ε4 non‐carriers (adjusted OR = 1.60, 95% CI: 1.04‐2.48, p = 0.034).ConclusionIndividuals with lower levels of sRAGE had an increased risk of 4‐year cognitive decline in APOE ε4 non‐carriers, indicating that the association between sRAGE and cognitive decline might depend on the APOE genotype. However, the specific mechanisms need to be further elucidated.