Association of SORL1 polymorphisms and SORL1-APOE ε4 interaction with risk of subjective cognitive decline and mild cognitive impairment in the Chinese population

Abstract

Background

Alzheimer's disease (AD) is a multifactorial disorder. The sortilin-related receptor 1 (SORL1) gene, which regulates the trafficking and recycling of amyloid precursor protein, has been reported to be associated with the development of AD.

Objective

This study investigated the impact of SORL1 polymorphisms (rs641120 and rs1784933) and their interaction with the apolipoprotein E (APOE) ε4 allele on AD preclinical stages—subjective cognitive decline (SCD) and mild cognitive impairment (MCI). We also explored the association between the rs641120 and serum biomarkers.

Methods

The study included 225 SCD, 131 MCI, and 62 normal controls (NC). Logistic regression models were utilized to assess genetic risks and interactions. Nonparametric tests or t-tests were employed to examine group differences stratified by protective genes in neuropsychological performance and biomarkers.

Results

The rs641120 A allele was associated with a lower risk of SCD and MCI, within AA genotype (OR = 0.575) and AG genotype (OR = 0.588). In MCI patients, the A allele was associated with lower levels of serum Aβ₁₋₄₂ and p-tau181. An interaction between SORL1 rs1784933 and the APOE ε4 allele was identified. In NC carrying ε4, AA is associated with higher risk of SCD (OR = 12.030, p = 0.029) and MCI (OR = 10.015, p = 0.044). In SCD patients without ε4, AA genotype is associated with lower risk of MCI (OR = 0.301, p = 0.006).

Conclusions

SORL1 polymorphisms influence SCD and MCI susceptibility and correlate with AD serum biomarkers. Additionally, we detected an interaction between SORL1 rs1784933 and the APOE ε4 genotype.