APOE ε4 allele elevates the expressions of inflammatory factors and promotes Alzheimer's disease progression: A comparative study based on Han and She populations in the Wenzhou area

Abstract

Objective: This study aimed to investigate the impact of apolipoprotein E 4 (APOE4) gene polymorphisms on the expressions of inflammatory factors and the progression of Alzheimer's disease (AD).

Methods: A total of 185 AD patients (the case group, 130 cases from the Han ethnic group and 55 cases from the She ethnic group) and 190 healthy individuals (the control group, 130 cases from the Han ethnic group and 60 cases from the She ethnic group) were recruited for our study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was conducted to detect APOE4 genotype and allele frequency. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expressions of inflammatory factors in plasma.

Results: In both Han and She populations, the frequency of ε3/4 and ε4/4 genotypes and the ε4 allele was significantly higher in the case group than that in the control group. ε3/4 and ε4/4 genotypes and the ε4 allele were the risk factors for AD. In both Han and She populations, the ε2/4, ε3/4 and ε4/4 carriers showed increased levels of TNF-α, IL-6, and IL-1β when compared with the ε2/2 + ε2/3 + ε3/3 carriers. The TNF-α, IL-6, and IL-1β levels were higher in the ε4/4 carriers than those in the ε2/4 and ε3/4 carriers, and ε2/4, ε3/4 and ε4/4 carriers in the case group exhibited increased levels of TNF-α, IL-6, and IL-1β when compared with the control group (P<0.05). Logistic regression analysis indicated that the ε3/4 genotype and TNF-α, IL-6, and IL-1β levels were associated with the susceptibility to AD in the Han population, while ε3/4 and ε4/4 genotypes and TNF-α, IL-6, and IL-1β levels were related to the susceptibility to AD in the She population.

Conclusions: The APOE4 ε4 allele may enhance susceptibility to AD and promotes the expressions of inflammatory factors in AD.

Keywords: Alzheimer's disease; Apolipoprotein E; Gene polymorphism; IL-6; IL-β; Inflammatory factor; TNF-α.