# Dissecting the Genetic Architecture of Cognitive Reserve and Resilience

> **NIH NIH P01** · WASHINGTON UNIVERSITY · 2021 · $188,550

## Abstract

Project 3 Project Summary
Aging populations worldwide, particularly in developed countries, face an increasing burden of
neurodegenerative diseases. The most common neurodegenerative disease is Alzheimer disease (AD), which
is characterized by protein misfolding and aggregation. One intriguing characteristic is the broad spectrum of
age at onset, even within specific risk groups (i.e, mutation carriers). Furthermore, the existence of resilient
individuals (individuals who are positive for known biomarkers or have a high burden of genetic risk variants
but do not exhibit symptoms), suggests that there are protective and disease-modifying genetic factors. The
goal of this Project is to identify variants and genes that confer resilience as well as novel protective and
modifying factors. We will use genetic data (GWAS, Exome-chip, Whole Exome Sequencing and Whole
Genome Sequencing) from resilient individuals and compare them with matched affected individuals to identify
protective and modifying genetic factors. The multi-factorial etiology and heterogeneity of AD may reveal itself
in racial or ethnic differences in overall AD risk and in putative risk or protective factors or in the progression of
neuropathology. For this reason, we will also determine if the modifier and protective variants, genes and
pathways also play a role in other races, especially in African Americans.

## Key facts

- **NIH application ID:** 10131746
- **Project number:** 5P01AG003991-38
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Carlos Cruchaga
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,550
- **Award type:** 5
- **Project period:** 1997-01-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10131746

## Citation

> US National Institutes of Health, RePORTER application 10131746, Dissecting the Genetic Architecture of Cognitive Reserve and Resilience (5P01AG003991-38). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10131746. Licensed CC0.

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