APOE ɛ4 Status and Plasma p-tau181 Levels May Influence Memory and Executive Function Decline in Older Adults Without Dementia

Abstract

Background: Elevated tau phosphorylation has been linked to the Apolipoprotein E (APOE) ɛ4 allele, which is considered one of the most significant genes related to Alzheimer’s disease (AD). However, it is uncertain whether the impact of increased plasma tau phosphorylated at threonine 181 (p-tau181) on memory and executive function decline would be greater among APOE ɛ4 carriers. Objective: To investigate the effects of plasma p-tau181 and APOE ɛ4 on memory and executive function. Methods: The longitudinal analysis included 608 older adults without dementia (aged 72±7 years; 47% female; follow-up period of 1.59±1.47 years) from the ADNI dataset, including 180 individuals with normal cognition and 429 individuals with mild cognitive impairment. Linear mixed-effects models were utilized to assess the contributions of APOE ɛ4 status and plasma p-tau181 to longitudinal changes in memory composite score and executive function composite score. Results: At baseline, the APOE ɛ4+/Tau+ group exhibited poorer performance in memory composite score and executive function composite score, and an elevated load of cerebrospinal fluid Aβ and tau pathologies. To further understand longitudinal changes, we compared groups directly based on plasma p-tau181 and APOE ɛ4 status (four groups: APOE ɛ4–/Tau–, APOE ɛ4–/Tau+, APOE ɛ4+/Tau–, APOE ɛ4+/Tau+). Both the memory composite score and executive function composite score showed a significantly greater decline in the APOE ɛ4+/Tau+ group than in all other groups. Conclusions: Our findings indicate that there is an interaction between plasma p-tau181 levels and APOE ɛ4 status, which contributes to the longitudinal changes of memory and executive function in older adults without dementia.