Moderating effect of 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 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 [C] Pittsburgh compound B-PET imaging to quantify Aβ deposition in the brain and blood sampling for genotyping. Sleep and circadian parameters were measured using actigraphy for 8 consecutive days.

Results: The ε4 allele had moderating effects on the associations of sleep latency (SL), mesor, and acrophase with cerebral Aβ deposition, and the interactions between ε4 status and SL and between ε4 status and acrophase remained significant after adjusting for multiple comparisons. In ε4 noncarriers, shorter SL, higher mesor, and advanced acrophase were associated with Aβ positivity. In contrast, 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 ε4 noncarriers.

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