Department of Anesthesiology, Weill Cornell Medicine, New York, NY, 10065, USA.
Center for Sleep and Circadian Biology, Department of Neurobiology, Northwestern University, Evanston, IL, 60208, USA.
Sci Rep. 2021 Apr 8;11(1):7797. doi: 10.1038/s41598-021-86255-6.
Reduced NREM sleep in humans is associated with AD neuropathology. Recent work has demonstrated a reduction in NREM sleep in preclinical AD, pointing to its potential utility as an early marker of dementia. We test the hypothesis that reduced NREM delta power and increased tauopathy are associated with shared underlying cortical molecular networks in preclinical AD. We integrate multi-omics data from two extensive public resources, a human Alzheimer's disease cohort from the Mount Sinai Brain Bank (N = 125) reflecting AD progression and a (C57BL/6J × 129S1/SvImJ) F2 mouse population in which NREM delta power was measured (N = 98). Two cortical gene networks, including a CLOCK-dependent circadian network, are associated with NREM delta power and AD tauopathy progression. These networks were validated in independent mouse and human cohorts. Identifying gene networks related to preclinical AD elucidate possible mechanisms associated with the early disease phase and potential targets to alter the disease course.
人类的非快速眼动睡眠减少与 AD 神经病理学有关。最近的研究表明，在临床前 AD 中 NREM 睡眠减少，这表明它可能作为痴呆的早期标志物具有潜在的应用价值。我们检验了这样一个假设，即减少 NREM 德尔塔功率和增加 tau 病变与临床前 AD 中共享的皮质下分子网络有关。我们整合了来自两个广泛的公共资源的多组学数据，一个是来自西奈山脑库的人类 AD 队列（N=125），反映 AD 的进展，另一个是（C57BL/6J×129S1/SvImJ）F2 小鼠群体，在该群体中测量了 NREM 德尔塔功率（N=98）。两个皮质基因网络，包括一个 CLOCK 依赖性昼夜节律网络，与 NREM 德尔塔功率和 AD tau 病变进展有关。这些网络在独立的小鼠和人类队列中得到了验证。确定与临床前 AD 相关的基因网络可以阐明与早期疾病阶段相关的可能机制，并为改变疾病进程提供潜在的靶点。
