# Linking Sleep Disruption to Tau Accumulation and Network Dysregulation in Early Alzheimer's Disease

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $847,144

## Abstract

Project Summary/Abstract:
Based on animal and limited human data, sleep disruption has been linked to decreased clearance and
increased production of b-amyloid and tau, proteins which in their aggregated forms represent the two
hallmark pathologies seen in Alzheimer’s disease. A number of different sleep parameters have also been
closely tied to memory consolidation and chronic sleep disruption increases the risk of memory impairment in
older individuals. However, despite data linking sleep disruption to Alzheimer’s disease pathology and
memory impairment, significant gaps remain in our understanding of how sleep disruption evolves over the
course of Mild Cognitive Impairment (MCI) and what aspects of sleep may be targets for intervention. In this
context, we propose to directly examine the evolution of sleep disruption in relation to the in vivo progression
of tau pathology, cognitive decline, and network dysfunction. Leveraging data that suggest that tau
accumulation may be quite rapid during prodromal Alzheimer’s disease, we will focus these studies on
individuals with MCI. We hypothesize that disrupted sleep architecture will be closely related to increased
neocortical tau pathology and cognitive impairment, both cross-sectionally and longitudinally. Further, we
hypothesize that sleep disruption leads to diminished connectivity in brain networks previously linked to
memory performance and cognitive decline, and that this network dysregulation may partially mediate the
effects of sleep disruption on cognition. Together, these studies will improve understanding on mechanistic
links between sleep, cognition, and Alzheimer’s disease. More broadly, the data from these studies will
critically inform the design of interventional studies modifying sleep in early Alzheimer’s disease by identifying
which specific aspects of disrupted sleep are most closely tied to b-amyloid and tau pathology (potential
therapeutic targets), assessing which aspects of sleep change over time in MCI, and the extent to which
longitudinal polysomnography and actigraphy can measure aspects of sleep disruption relevant to Alzheimer’s
disease.

## Key facts

- **NIH application ID:** 9988329
- **Project number:** 5R01AG062667-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** JASMEER P CHHATWAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $847,144
- **Award type:** 5
- **Project period:** 2019-08-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988329

## Citation

> US National Institutes of Health, RePORTER application 9988329, Linking Sleep Disruption to Tau Accumulation and Network Dysregulation in Early Alzheimer's Disease (5R01AG062667-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9988329. Licensed CC0.

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