Marked sleep disruption has long been recognized as a prevalent feature of Alzheimer's disease. However, a corpus of new data suggests that sleep abnormalities are not simply a symptom of aging and Alzheimer's disease, but an intimate and bi-directional component of their pathophysiology that further contributes to impairments in long-term memory consolidation. Despite these emerging links, the pathological role of tau protein aggregation in disrupting human NREM sleep physiology remains un-investigated, as does the potential consequence of such disruption for explaining impaired long-term memory consolidation in Alzheimer's disease. Moreover, the longitudinal inter-relationship between tau aggregation, NREM sleep physiology deterioration, and the impairment in hippocampal memory that typifies Alzheimer's disease, is also unknown. Addressing these questions, this proposal will test the hypothesis that early accumulation of tau in the human medial temporal lobe selectively impairs NREM sleep oscillations, thereby diminishing long-term memory consolidation and associated aspect of cognition, both cross-sectionally and longitudinally. Such findings may help identify a unique mechanistic pathway (sleep disruption) through which Alzheimer's disease pathology transacts memory impairment, and further define a new therapeutic target (sleep restoration) for intervention in aging and Alzheimer's disease. Additionally, such data would motivate a greater sensitivity of physicians to inquire about, diagnose and treat sleep difficulties across all ages. More generally, support for our hypothesis would argue for improved public health policies advocating for sufficient quality sleep throughout adulthood?a memorandum that may lower dementia risk and maintain cognitive health across the populous.

Public Health Relevance

This proposal seeks to test the hypothesis that early accumulation of tau in the human medial temporal lobe selectively impairs NREM sleep oscillations, thereby diminishing long-term memory, both cross-sectionally and longitudinally. Such findings may help identify a unique mechanistic pathway (sleep disruption) through which Alzheimer's disease pathology transacts memory impairment, and define a new therapeutic target (sleep restoration) for intervention in aging and Alzheimer's disease.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Multi-Year Funded Research Project Grant (RF1)
Project #
1RF1AG054106-01A1
Application #
9449097
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mackiewicz, Miroslaw
Project Start
2017-09-15
Project End
2022-06-30
Budget Start
2017-09-15
Budget End
2022-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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Krause, Adam J; Simon, Eti Ben; Mander, Bryce A et al. (2017) The sleep-deprived human brain. Nat Rev Neurosci 18:404-418
Mander, Bryce A; Winer, Joseph R; Walker, Matthew P (2017) Sleep and Human Aging. Neuron 94:19-36