Moderating effect of APOE ε4 on the relationship between sleep-wake cycle and brain ß-amyloid
Moderating effect of APOE ε4 on the relationship between sleep-wake cycle and brain ß-amyloid
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DOI：
10.1212/wnl.0000000000005193
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发表时间：
2018-03-27
期刊：
影响因子：
9.9
通讯作者：
Lee, Dong Young
中科院分区：
文献类型：
--
作者：
Hwang, Jeong Yeon;Byun, Min Soo;Lee, Dong Young
目的明确认知正常(CN)老年人睡眠-觉醒周期与脑内淀粉样蛋白(Ass)沉积的关系，主要关注APOE-epsilon 4的调节作用。方法本研究包括133名参加韩国阿尔茨海默病早期诊断和预测研究的CN老年人。所有参与者都接受了[C-11]匹兹堡复合B-PET成像，以量化Ass在脑中的沉积，并采集血液进行APOE基因分型。结果APOE epsilon 4等位基因对睡眠潜伏期(SL)、中位相和峰相与脑Ass沉积的关系具有调节作用，调整多重比较后，APOE epsilon 4状态与SL、APOE epsilon 4状态与顶相之间的交互作用仍显著。在APOE epsilon 4非携带者中，较短的SL、较高的中位数和较高的顶相与Ass阳性有关。相反，APOE epsilon 4携带者表现出顶相延迟与Ass积累的关系，接近但未达到显著水平。在Bonferroni校正后，APOE epsilon 4非携带者的短SL和高中位数与Ass阳性之间的相关性仍然显著。结论APOE epsilon 4等位基因可能在CN老年人睡眠-觉醒周期与Ass蓄积的关系中起调节作用。因此，在设计相关研究或干预措施时，需要将apoE epsilon 4状态作为一个关键因素来考虑。
ObjectivesTo 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.MethodsThe 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.ResultsThe 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.ConclusionsOur 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.