Differential Effects of the Interaction Between the Education and APOE ε4 Allele on Amyloid-beta Retention and Memory Performances in Cognitively Normal Older Adults and Alzheimer's Disease Patients

Abstract

Background: Despite the effect of education and APOE ε4 allele on amyloid-beta (Aβ) retention and memory, previous studies have not dealt with an interaction between two factors on Aβ deposition and memory function in the course of Alzheimer’s disease (AD). Objective: To evaluate education by APOE ε4 allele interactions for Aβ retention and neuropsychological test scores in cognitively normal older adults without Aβ deposition [CN(Aβ-), n=45] and Alzheimer’s disease patients with Aβ retention [AD(Aβ+), n=33]. Methods: Multiple regression analyses (adjusted for age, gender) were conducted to examine the effects of education, APOE ε4 allele, and the interaction between the two factors on global, regional Aβ load quantified using [18F]flutemetamol standardized uptake value ratio with the pons as a reference region, and on neuropsychological test scores in each group. Results: The interaction between education and APOE ε4 allele had an effect on amyloid load in parietal lobes (uncorrected p<0.05) and striatum (Bonferroni corrected p<0.05) in each CN(Aβ-) and AD(Aβ+). There was also an interaction effect of education and APOE ε4 allele on the memory performance in each CN(Aβ-) and AD(Aβ+) (uncorrected p<0.05). APOE ε4 carriers of both groups showed opposing slopes with each other in the correlation between the education years and β load, memory performance. Conclusion: The current results suggest a possible explanation of the differential effects of education and APOE ε4 allele interactions on AD pathology and memory function at the beginning and end of AD progress. However, further study with a validating cohort is needed for confirming this explanation.