# Systems Genetic Analysis of Cognitive Resilience Using Multi-Parent Crosses

> **NIH NIH RF1** · JACKSON LABORATORY · 2021 · $421,114

## Abstract

PROJECT SUMMARY/ABSTRACT
Cognitive resilience is a phenomenon whereby individuals are resistant to the most damaging effects of aging
on cognition – individuals that maintain normal cognitive function despite being long-lived (e.g. centenarians)
are said to exhibit high cognitive reserve or resilience depending on the conceptual definitions (see Reserve
and Resilience NIA Consortium). Genetic factors promoting cognitive reserve and resilience may thus provide
key targets for treatment and prevention of cognitive decline across a spectrum of age-related dementias
including Alzheimer’s disease (AD) and Alzheimer’s disease related dementias (ADRD). Our overall objective
is to identify drivers of cognitive reserve and resilience by using network approaches to integrate data
collected from Diversity Outbred (DO) mouse models with human data. Data generated as part of the parent
award indicates that regional changes in cell-type composition may be a significant contributing factor in
determining individual differences in cognitive reserve and resilience. Recent advances in brain-wide spatial
analyses of correlates of brain reserve and resilience, and particularly the advent of high throughput platforms
for large-scale immunohistochemistry (IHC) to label multiple cell types throughout hundreds of mouse brains,
now make it feasible to assess region and cell type specific hallmarks of cognitive reserve and resilience and
clinically relevant traits in the same mice as used for assessing cognition, motor, sleep, and metabolic
symptoms, representing a powerful complement to our ongoing work and adding a new layer of information
regarding regional and cell-type specificity to our multi-scale network model. With the proposed supplement,
we will be able to identify changes in specific brain regions and cell types associated with cognitive reserve
and their relationship to transition towards Alzheimer’s disease and age-related dementias. This project will
deliver novel brain regions and cell types for promoting healthy brain aging (reserve) and resilience to aging.
We will annotate, curate, and rapidly disseminate the data to the broad scientific community prior to
publication to maximize the usability of these data for meta-analysis and systems biology research.

## Key facts

- **NIH application ID:** 10330619
- **Project number:** 3RF1AG063755-01S1
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** CATHERINE COOK KACZOROWSKI
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $421,114
- **Award type:** 3
- **Project period:** 2019-09-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10330619

## Citation

> US National Institutes of Health, RePORTER application 10330619, Systems Genetic Analysis of Cognitive Resilience Using Multi-Parent Crosses (3RF1AG063755-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10330619. Licensed CC0.

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