Faculty Proceedings, Presentations, Speeches and Lectures

Title

APOE ε4 as a Predictor of Tauopathies Independent of β-Amyloid

Event Title

2021 Alzheimer's Association International Conference

Event Location

Virtual

Document Type

Paper

Presentation Date

7-26-2021

Date Range

2021-07-26 to 2021-07-30

Description

Background: Due to the failure of clinical trials that target amyloid β and findings that suggest tau’s role in Alzheimer’s Disease (AD) atrophy and cognitive decline, the investigation of tau-pathology in AD is needed. While studies have investigated the effect of APOE ε4 on tau-pathology in mouse models, few have examined the relationship in humans, as well as tau’s role on cognitive decline as a mechanism independent of amyloid β deposition. The aim will be to examine the roles of tau in AD, as an independent pathway.

Method: Utilizing the National Alzheimer’s Coordinating Center (NACC) database, our sample included those determined with AD, as defined by NACC derived variables. Among participants (n= 5391,Mage= 73, SD=10.5) ε4 carriers accounted for 42%. A separate longitudinal sample (n=108, Mage= 70, SD=9.80) was used to determine cognitive decline as measured by the MoCA.

Result: The ANCOVA showed a significant effect of APOE carrier status on neurofibrillary tangles after controlling for neuritic plaques, F(1,5390) = 5643.617, p<.001, partial η2=.512 and separately, after controlling for Thal amyloid phases, F(1,2632) =4809.032, p<.001, partial η2=.646. The regression model showed covariates including sex, race, ethnicity, age, education, and language did not contribute significantly to the model, F(6,102) =2.051, p<=0.66 and accounted for 10.8% of the variation on MoCA scores. Introducing APOE carrier status explained 16.5% of the variation of MoCA and was significant in change, F(1,101) =6.891, p=.010. While addition of all neuropathies explained 32.9% of the model, F(3,98) =7.979, p<.001, post hoc T-tests revealed that only neurofibrillary tangles had a significant effect on cognitive decline, demonstrating a negative relationship.

Conclusion: These results indicate that the neuropathological effects of APOE ε4 are demonstrated with or without amyloid β deposition, suggesting that apoE may act through tau-pathways independently. Additionally, while the relationship between APOE ε4 and neuropathology predicts cognitive decline, NFT is the primary driver of cognitive decline in Alzheimer's Disease, while amyloid β deposition has no significant effect.

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