Association of plasma phosphor-tau181 with Aβ levels may vary by APOE ε4 status and sex among non-demented old adults

Abstract

BackgroundTo evaluate the relationship between blood tau phosphorylated at threonine 181 (p-tau181) levels and β-amyloid (Aβ) levels, this study took the potential role of sex differences and apolipoprotein E (APOE)-ε4 status into account. MethodsWe examined 620 participants with normal cognition (n = 178) and mild cognitive impairment (n = 442). Three-way interactions between sex, APOE ε4 status, and the levels of plasma p-tau181 were examined with linear regression models for Aβ levels adjusting for age, education, and diagnosis. The correlation analysis was performed to detect the association of the levels of plasma p-tau181 with brain Aβ stratified for APOE status and sex. ResultsBlood p-tau181 levels were higher in APOE ε4+ participants as compared to APOE ε4 – participants (p < 0.001). A comparison of APOE ε4 status within each gender showed that APOE ε4 carriers had higher levels of plasma p-tau181 and amyloid-β than APOE ε4 noncarriers in both men and women (p < 0.001). In sex/APOE-stratified analyses, individuals with the APOE ε4 allele showed stronger correlations between plasma p-tau181 and brain Aβ levels in both females (r = 0.49, p < 0.001 for APOE ε4 carriers vs r = 0.28, p < 0.001 for APOE ε4 noncarrier.) and males (r = 0.34, p < 0.001 for APOE ε4 carriers vs r = 0.21, p = 0.04 for APOE ε4 noncarriers.). In interactive analysis, the association of plasma p-tau181 and Aβ levels was significant in the female APOE ε4 carriers (p < 0.003). DiscussionAPOE ε4 status and female sex interact to impact the correlation between plasma p-tau181 and Aβ levels. Although the APOE ε4 genotype is one of the most important risky genes for AD, sex differences may also modify the degree of risk at critical times among non-demented older adults.