UC Berkeley

Impaired sleep is a frequent symptom affecting patients with Alzheimer’s disease (AD). Recent work has shown that sleep disruption occurs very early in the progression of AD, before the presence of significant cognitive decline. The accumulation of tau neurofibrillary tangles and β-amyloid (Aβ) plaques, the hallmark pathologies of AD, have been shown to impact sleep electrophysiology in rodent models. Furthermore, experimental disruption of sleep accelerates AD progression, suggesting that this relationship is bi-directional. With the recent advent of PET radiotracers that bind to in vivo tau and Aβ in the human brain, it is now possible to study how the presence of these proteins affect sleep physiology in healthy older people. Is disrupted sleep an early marker of the pathogenesis of AD? In this dissertation, I address this question by investigating associations between a diverse set of sleep metrics and PET-measured tau and Aβ burden in cognitively healthy older adults. Chapter 1 demonstrates that greater tau and Aβ are associated with distinct impairments in sleep oscillatory signatures, and that self-reported changes in sleep across the lifespan are predictive of pathological burden in late-life. Chapter 2 utilizes a longitudinal design to establish that impairments in both micro-electrophysiological and macro-architectural measures of sleep predict the subsequent rate of Aβ accumulation. Chapter 3 describes associations between tau and Aβ and real life patterns of sleep behavior, and shows that individuals with greater pathological burden are worse at estimating their own sleep quality. Together, these data illustrate the ways that sleep, measured objectively and subjectively, in the sleep lab and at home, is affected in the earliest stages of AD. These findings indicate the sensitivity of human sleep physiology to AD, and suggest that sleep may provide a non-invasive biomarker of tau and Aβ burden in cognitively normal older adults. Most importantly, while more work is needed to confirm these findings, these relationships offer the possibility that improving sleep quality may slow the progression of AD.