Moderating effect of APOE ε4 on the relationship between sleep-wake cycle and brain β-amyloid.

OBJECTIVES

To clarify the relationships between sleep-wake cycle and cerebral β-amyloid (Aβ) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the APOE ε4 allele.

METHODS

The present study included 133 CN older adults who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer's Disease cohort. All participants underwent [11C] Pittsburgh compound B-PET imaging to quantify Aβ deposition in the brain and blood sampling for APOE genotyping. Sleep and circadian parameters were measured using actigraphy for 8 consecutive days.

RESULTS

The APOE ε4 allele had moderating effects on the associations of sleep latency (SL), mesor, and acrophase with cerebral Aβ deposition, and the interactions between APOE ε4 status and SL and between APOE ε4 status and acrophase remained significant after adjusting for multiple comparisons. In APOE ε4 noncarriers, shorter SL, higher mesor, and advanced acrophase were associated with Aβ positivity. In contrast, APOE ε4 carriers showed a relationship between delayed acrophase and Aβ accumulation that approached but did not reach significance. After the Bonferroni correction, the associations of shorter SL and higher mesor with Aβ positivity remained significant for APOE ε4 noncarriers.

CONCLUSIONS

Our findings suggest that the APOE ε4 allele may act as a moderator in the relationship between the sleep-wake cycle and Aβ accumulation in CN older adults. Thus, APOE ε4 status needs to be considered as a key factor when designing related research or interventions.