# Identifying the molecular systems, networks, and key molecules that underlie cognitive resilience

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2021 · $224,880

## Abstract

ABSTRACT
The proposed study: Identifying the molecular systems, networks, and key molecules that underlie cognitive
resilience is in response to
RFA-AG-17-061.
The overall goal of the proposed study is to identify the
molecular networks underlying resilience to AD, other age-associated neuropathologies and risk
factors associated with resilience.
The proposal is highly responsive to the RFA in that it is focused on the
function of networks supporting cognitive resilience. Specifically, we will
generate high-dimensional molecular
data, to which we will apply systems biology approaches, and then integrate these with measures of resilience
that rely on longitudinal cognitive data and assays of age-related neuropathologies. A key outcome of this
research will be linking environmental, lifestyle and experiential factors to specific molecular networks. In
addition to protein validation in humans, we will utilize living human brain networks as a validation “model
system”. We are able to do this, b
ecause for the first time our omics will be acquired from persons who
previously provided fMRI data. Therefore, we can provide a unified perspective on the basis of resilient brain
function in molecular and brain networks, which provides high confidence validated molecules and networks
driving resilience to AD and age-related neuropathologies in humans.
Our main resources for the proposed study are two longitudinal studies of aging, which provide neuroimaging,
omic detailed neuropathology, longitudinal cognition scores and a quantitative measure of resilience for each
person. From these cohorts, in Aim 1 we will acquire RNAseq and TMT proteomics (9000+ measured
proteins) from regions of the brain whose molecular structure varies in synchrony with a continuous measure of
resilience, based on MRI of this cohort. After identifying the molecular systems active in these regions, we will
(Aim 2)
 infer the networks contained within each molecular system, the connections between molecular
systems, and the connections between molecular systems and resilience. Given the limitations of animal
models in validating cognitive phenotypes, we utilize a unique resource to validate the gene and protein
networks found to be associated with resilience. We will (Aim 3) use dynamic fMRI-based brain networks,
previously acquired from the same individuals to validate the post-mortem molecular networks with this close
proxy of cognitive function. Thus the proposal brings to bear several major perspectives on resilience –
longitudinal cognition, neuropathology, multiple omics and neuroimaging to identify novel networks and targets
to stimulate resilience, producing a strong and sustained impact on the field.

## Key facts

- **NIH application ID:** 10229602
- **Project number:** 5R01AG057911-05
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Christopher A. Gaiteri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $224,880
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10229602

## Citation

> US National Institutes of Health, RePORTER application 10229602, Identifying the molecular systems, networks, and key molecules that underlie cognitive resilience (5R01AG057911-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10229602. Licensed CC0.

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