# Elucidating the role of circadian-gated cognitive disruption in Alzheimer’s disease pathogenesis

> **NIH NIH F99** · OHIO STATE UNIVERSITY · 2020 · $33,787

## Abstract

Project Abstract
As the portion of the population that is aged 65 and older rapidly increases in parallel with increases in life
expectancy, there is an urgent need to address the disease states that affect the elderly population. One of
these—perhaps the most devastating—is Alzheimer’s disease (AD). In addition to the cognitive impairments that
underlie AD, these patients suffer with dysregulation of their circadian timing system including cognition. This
timing system is vital to health at the cellular level and to overall physiology; hence, circadian disruptions can
have profound negative effects on health, further exacerbating the AD symptomology. Specifically, circadian-
gated cognition is the inherent 24-hour cycles of regulation that underlie efficacy of learning and memory across
the day. Along these lines, the goal of this work is to better understand the molecular components in the brain
that mediate deterioration of circadian-gated cognition in AD. Utilizing an innovative set of approaches ranging
from behavioral testing to in vivo cranial window multiphoton imaging, this work will address the following specific
aims. My dissertation work thus far (Aim 1) has shown that circadian-gated cognitive deficits are present in a
mouse model of rapid amyloid deposition and that there are disruptionin core clock genes that generate circadian
timing may mediate these. Circadian timing regulates a plethora of cellular processes, including the functionality
of the mitogen activated protein kinase (MAPK) pathway. Furthermore, the MAPK pathway is essential to
circadian-gated cognitiveprocesses and its activation has been shown to be disrupted in AD. Thus, in next phase
of my work (F99, Aim 2), I will test if the dysregulation of MAPK pathway activation is the mechanistic link
governing disruption of circadian-gated cognition in a model of AD. In addition to profiling the disruption of MAPK
activity in AD, I will attempt to restore activity of the MAPK pathway to baseline, thus rescuing circadian-gated
cognition. Upon the completion of my dissertation work, I plan to complete a postdoctoral fellowship (K00, Aim
3) where I will aim to study the genetic basis of sleep in parallel with the genetic mechanisms underlying sleep
dysfunction in neurodegenerative disorders. This postdoctoral work will complement my training in circadian
biology and neurodegeneration ultimately providing me the necessary tools and skill to address questions
regarding the interplay of sleep and circadian rhythmicity disruption in neurodegenerative.

## Key facts

- **NIH application ID:** 10071551
- **Project number:** 1F99NS118743-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Anisha Kalidindi
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,787
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071551

## Citation

> US National Institutes of Health, RePORTER application 10071551, Elucidating the role of circadian-gated cognitive disruption in Alzheimer’s disease pathogenesis (1F99NS118743-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10071551. Licensed CC0.

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