Characterizing sleep brain dynamics associated with Alzheimer's disease pathology and progression in humans using EEG source localization and PET

项目总结 阿尔茨海默病(AD)是一种神经退行性疾病，是导致痴呆症的最常见原因。广告 包括一系列的病理生理过程，包括淀粉样β蛋白、神经原纤维的积累 Tau缠结、神经元变性和神经炎症。现在有强有力的证据表明 睡眠期间脑动力学的变化与潜在的神经病理学的发展有关。上一首 研究检验了头皮脑电特征与PET粗略汇总测量之间的相关性 淀粉样蛋白和tau蛋白，但神经电生理学和淀粉样蛋白/tau蛋白病理之间更精确的联系 站点级别、区域级别和网络级别尚未进行详细分析。在空间上和空间上描述这些 功能上特定的模式对于使用睡眠相关生物标记物进行AD的未来早期检测至关重要， 开发睡眠干预措施以减缓疾病进展，并进行电生理监测 以淀粉样蛋白/tau为中心的治疗。与此同时，在过去的几年里，我们的团队取得了显著的成就 脑电源定位方法的进展，使大脑电流能够定位在皮质和 皮质下区域的分辨率可与正电子发射计算机断层扫描和功能磁共振成像媲美。在这个项目中，我们建议 测量人类睡眠期间的高密度脑电，以及PET和MRI，跨越AD的各个阶段 临床前到轻度认知障碍到轻度阿尔茨海默病。

PROJECT SUMMARY Alzheimer’s disease (AD) is a neurodegenerative disease that is the most common cause of dementia. AD encompasses a range of pathophysiologic processes including accumulation of amyloid-beta, neurofibrillary tau tangles, neuronal degeneration, and neuroinflammation. There is now strong evidence suggesting that changes in brain dynamics during sleep are related to development of underlying neuropathology. Previous studies have examined correlations between scalp EEG features and coarse summary measures of PET amyloid and tau, but the more precise link between neural electrophysiology and amyloid/tau pathology at site-, region-, and network-levels has not yet been analyzed in detail. Characterizing these spatially and functionally specific patterns is critical for future early detection of AD using sleep-related biomarkers, development of sleep interventions to slow disease progression, and electrophysiological monitoring of amyloid/tau-centric treatments. Meanwhile, over the past several years, our group has made significant advances in EEG source localization methods that enable localization of cerebral currents in cortical and subcortical regions at a resolution that is comparable to PET and fMRI. In this project, we propose to measure high-density EEG during sleep in humans, alongside PET and MRI, across the stages of AD from Preclinical to Mild Cognitive Impairment to mild AD dementia.