# Relationships between tau pathology, sleep physiology and memory in aging

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $18,491

## Abstract

Project Summary
Recent work suggests that disrupted sleep is a bi-directional feature in the pathological progression of
Alzheimer’s disease. Human studies have focused on β-amyloid (Aβ) accumulation, which has been shown to
predict subjective and objective declines in sleep quality. It remains unknown whether tau protein, the other
primary pathological feature of Alzheimer’s disease, contributes to sleep disruption. In rodent models,
aggregated tau predicts abnormalities in non-rapid eye movement (NREM) sleep physiology. This finding is
functionally relevant, due to the known role of NREM sleep oscillations in supporting long-term memory
consolidation. Specifically, the strength of coordinated coupling of three NREM sleep oscillations (slow waves,
spindles, and sharp-wave ripples), which occurs within the human medial temporal lobe (MTL), has been
demonstrated to predict overnight memory retention. MTL is known to be one of the first brain regions to
accumulate tau pathology, before the onset of Alzheimer’s disease symptomology. Given this anatomical
overlap, we hypothesize that MTL tau burden will predict disrupted coordination of NREM sleep oscillations in
cognitively normal older adults at risk for Alzheimer’s disease. We further predict that this tau-induced disruption
of oscillatory coupling will be associated with impaired long-term memory consolidation. By combining (i) in vivo
brain imaging of tau pathology (18F-AV1451 PET), (ii) overnight high-density EEG, (iii) weeklong wristwatch
actigraphy measures of sleep, and (iv) sensitive measures of memory consolidation, this proposal aims to
characterize associations between tau and sleep physiology, and their impact on hippocampus-dependent
memory in the context of preclinical Alzheimer’s disease. Aim 1 will determine whether early tau accumulation
in MTL is associated with the disruption of NREM sleep oscillations, and if this disruption results in failed memory
consolidation. Aim 2 seeks to determine whether wristwatch actigraphy measures of sleep quality across multiple
nights may serve as a sensitive and specific marker of tau burden. By elucidating the relationship between tau
pathology and multiple measures of sleep, these experiments may provide important preliminary data for
developing sleep-based therapies targeting Alzheimer’s disease prevention and treatment.

## Key facts

- **NIH application ID:** 9972736
- **Project number:** 5F31AG063428-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Joseph Robert Winer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $18,491
- **Award type:** 5
- **Project period:** 2019-05-20 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972736

## Citation

> US National Institutes of Health, RePORTER application 9972736, Relationships between tau pathology, sleep physiology and memory in aging (5F31AG063428-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9972736. Licensed CC0.

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