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

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.