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

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2021 · $437,163

## 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, because 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
and producing a strong and sustained impact on the field.

## Key facts

- **NIH application ID:** 10729301
- **Project number:** 7R01AG057911-06
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** Christopher A. Gaiteri
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $437,163
- **Award type:** 7
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10729301

## Citation

> US National Institutes of Health, RePORTER application 10729301, Identifying the molecular systems, networks, and key molecules that underlie cognitive resilience (7R01AG057911-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10729301. Licensed CC0.

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