# Systems Genetics Analysis of Sex Differences in Alzheimer's Disease

> **NIH NIH R01** · JACKSON LABORATORY · 2022 · $1,235,110

## Abstract

PROJECT SUMMARY
Our proposed research aims to identify sex-specific genetic drivers of neuropathologic, cognitive, and
metabolic phenotypes of Alzheimer’s disease by integrating longitudinal behavioral and molecular data from
AD mice with genetic, genomic and clinical data from human cohorts. We will leverage a newly generated
mouse population that incorporates high-risk familial AD (FAD) mutations on a genetically diverse background
(BXD panel) to identify modifiers that contribute to AD resilience in this ‘humanized’ mouse population. In
parallel, we will incorporate cutting-edge single-cell omic approachs to generate a molecular atlas of human
brains from carriers of FAD mutations (in APP, PSEN1 and PSEN2) and non-carriers with sporadic AD. By
combining and validating analyses in both mouse and human datasets, we expect to find molecular candidates
that robustly contribute to sex-specific variation in symptoms of AD. We will further validate these candidates
using unparalleled in vivo mouse technology to not only empircally assess their role in sex-specific
mechanisms of disease, but also to evaluate sex X genotype X treatment interactions in a subset of candidates
(i.e., Apoe) to inform more personalized therapeutic approaches. The approach we propose benefits from the
enhanced discovery power and value of existing human genetics resources and novel, precision AD mouse
models across multiple institutions to investigate the mechanisms of sex differences in AD.

## Key facts

- **NIH application ID:** 10476515
- **Project number:** 5R01AG074012-02
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Oscar Harari
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,235,110
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476515

## Citation

> US National Institutes of Health, RePORTER application 10476515, Systems Genetics Analysis of Sex Differences in Alzheimer's Disease (5R01AG074012-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10476515. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*