Moderating effect of APOE epsilon 4 on the relationship between sleep-wake cycle and brain ss-amyloid

Objectives To clarify the relationships between sleep-wake cycle and cerebral ss-amyloid (A ss) deposition in cognitively normal (CN) older adults, focusing primarily on the moderating effects of the APOE epsilon 4 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-11]Pittsburgh compound B-PET imaging to quantify A ss 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 epsilon 4 allele had moderating effects on the associations of sleep latency (SL), mesor, and acrophase with cerebral A ss deposition, and the interactions between APOE epsilon 4 status and SL and between APOE epsilon 4 status and acrophase remained significant after adjusting for multiple comparisons. In APOE epsilon 4 noncarriers, shorter SL, higher mesor, and advanced acrophase were associated with A ss positivity. In contrast, APOE epsilon 4 carriers showed a relationship between delayed acrophase and A ss accumulation that approached but did not reach significance. After the Bonferroni correction, the associations of shorter SL and higher mesor with A ss positivity remained significant for APOE epsilon 4 noncarriers. Conclusions Our findings suggest that the APOE epsilon 4 allele may act as a moderator in the relationship between the sleep-wake cycle and A ss accumulation in CN older adults. Thus, APOE epsilon 4 status needs to be considered as a key factor when designing related research or interventions.