APOE ε4 status and plasma p-tau181 interact to influence cognitive performance among non-demented older adults

In this study, we aimed to investigate the relationships among plasma p-tau181, APOE ε4, and cognitive performance in non-demented elderly individuals.

We used individuals (n = 630) with cognitive normal (CN, n = 182) and mild cognitive impairment (MCI, n = 448). Multiple linear regression models were performed to test the effects of APOE ε4 × plasma p-tau181 interaction on MMSE, CDR-SOB, ADAS-cog13, and RAVLT immediate recall. All models adjusted for age, sex, and education.

In total, our study comprised 630 samples including 364 APOE ε4 non-carriers and 266 APOE ε4 carriers. In APOE ε4 carriers, plasma p-tau181 was significantly associated with MMSE (B = -0.04, p = 0.003), ADAS-Cog13 (B [unstandardized coefficient] = 0.21, p < 0.001), CDR-SB (B = 0.02, p = 0.003) and RAVLT immediate recall ((B = -0.17, p = 0.035). After correcting for Aβ status and diagnosis, the interaction between APOE ε4 and plasma p-tau181 was significant or marginally significant associations for RAVLT immediate recall (p = 0.076), MMSE (p = 0.011), CDR (p = 0.008), and ADAS-Cog13 (p < 0.001).

Our findings suggested that plasma p-tau181 levels predicted cognitive performance among non-demented older adults, but only in the APOE ε4 carriers.