# Slow-wave activity as a modifier of the progression of neurodegeneration in Alzheimer's disease

> **NIH NIH RF1** · HARVARD MEDICAL SCHOOL · 2021 · $194,995

## Abstract

Sleep-wake disruptions and cognitive impairments are prevalent and disabling features of Alzheimer's disease
(AD). AD patients exhibit profound sleep disturbances including disruption of non-rapid eye movement (NREM)
sleep. A major restorative feature of NREM sleep, which is also associated with proper cognitive functioning, is
slow-wave activity (SWA). Recent findings suggest a causal relationship between impaired generation of SWA
during sleep and AD pathogenesis including extracellular accumulation of the amyloid-β (Aβ) peptide and
neuronal dysfunction. While evidence indicates that cortical-thalamic loops regulate SWA, the exact cellular
and molecular mechanisms for impaired SWA in AD are unknown. Thus, a need exists to characterize the cells
and molecular mechanisms responsible for SWA generation to reduce the impairments in SWA and
pathogenesis of AD. We propose studies that will elucidate the sleep state related mechanisms by which SWA
protects against AD. Studies using AD animal models suggest that inhibitory neurotransmission is impaired
during periods of SWA. The overall objective of this proposal is to identify and stimulate specific SWA
modulating interneuronals to determine which cells restore SWA and mitigate AD-related pathology using an
established AD mouse model. Herein, we propose to employ optogenetics and chemogenetics to control
neuronal circuits aimed to restore SWA and slow AD progression. Thus, our findings will determine the cellular
and molecular relationships between sleep and AD, with the targeting of interneurons during specific periods of
sleep as a novel therapeutic approach.

## Key facts

- **NIH application ID:** 10205286
- **Project number:** 3RF1AG061774-01S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Brian J Bacskai
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $194,995
- **Award type:** 3
- **Project period:** 2019-04-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205286

## Citation

> US National Institutes of Health, RePORTER application 10205286, Slow-wave activity as a modifier of the progression of neurodegeneration in Alzheimer's disease (3RF1AG061774-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10205286. Licensed CC0.

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