APOE interacts with tau PET to influence memory independently of amyloid PET in older adults without dementia

Introduction: Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition. Methods: For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (A beta) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for A beta, including interactions with APOE epsilon 4-carrier status. Results: Adjusting for tau PET, A beta was not associated with cognition and did not interact with APOE. In contrast, adjusting for A beta PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in epsilon 4-carriers, even among A beta-negative individuals. Discussion: Findings suggest that APOE may interact with tau independently of A beta and that elevated MTL tau confers negative cognitive consequences in A beta-negative epsilon 4 carriers.

Automated summary

The study revealed that APOE may interact with tau independently of Aβ, and elevated MTL tau levels have negative cognitive consequences in Aβ-negative ε4 carriers.