# Circadian Regulation of Memory During Alzheimer's Disease Pathogenesis

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $393,438

## Abstract

Project Summary
 We propose to investigate the association between circadian system dysfunction, cognition, and
Alzheimer’s disease (AD) pathogenesis. Originally, most circadian system changes were thought to be driven
by the disease process. Recently, however, there is a growing realization that long-term circadian dysfunction
has serious health consequences and may even precede the clinical onset of memory deficits in AD. This field
is embarking on a paradigm shift that the circadian system may directly influence AD pathogenesis.
Specifically, disruption of the circadian system central pacemaker, the suprachiasmatic nucleus (SCN), may
contribute to the observed fragmented circadian system dysregulation in preclinical AD. The goal of this project
is to test the hypothesis that poor circadian rhythms mediated by a dysfunctional central clock directly influence
AD pathogenesis. The following aims will test this hypothesis: (1) examine the effects of altered SCN function
on downstream hippocampal-dependent behavioral, physiological, and molecular rhythms; (2) examine the
effects of chronic aberrant SCN signaling on amyloidogenic processes; (3) examine the effects of a circadian
intervention on AD pathogenesis. We will combine cutting-edge in vivo optogenetic techniques with
sophisticated neurophysiological measures to examine the dynamic regulation of learning and memory
processes by the circadian system. Circuit-specific optogenetic manipulation of circadian system function while
assaying cognitive functions represents a highly novel and methodologically unique approach. We will decipher
a mechanistic link between circadian system dysregulation and cognitive decline in AD. With this project, we
are well-poised to uncover new insights into the complex biological mechanisms associated with AD. Because
sleep-wake and circadian disruptions are major causes of morbidity and institutionalization among AD patients,
we hope that these studies may lead to effective interventions to forestall disease progression, which would
also lessen caregiver burden and decrease financial care costs associated with progressing dementia.

## Key facts

- **NIH application ID:** 9977075
- **Project number:** 5R01AG063834-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Geraldine J. Kress
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,438
- **Award type:** 5
- **Project period:** 2019-07-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9977075

## Citation

> US National Institutes of Health, RePORTER application 9977075, Circadian Regulation of Memory During Alzheimer's Disease Pathogenesis (5R01AG063834-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9977075. Licensed CC0.

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