# Sex-Specific Genetic Drivers of Alzheimer's Disease Endophenotypes

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $780,953

## Abstract

Abstract
As the population ages, late-onset Alzheimer’s disease (AD) is becoming an increasingly important public
health issue. AD disproportionately affects women. Of the more than 5 million people in the United States
afflicted with this disease, two-thirds are women. Women with AD have more neuropathology than men with
AD, have more severe cognitive symptoms, and more severe neurodegeneration, suggesting that the disease
affects male and female brains in different ways. Thus, a focus on sex differences in AD is essential to move
the field towards effective interventions. The identification of sex-specific genetic drivers of AD and AD-related
endophenotypes could transform the way treatments are administered and be a critical step towards
personalized interventions for AD. Research from both our group and others has begun to uncover genetic
factors that explain some of the observed differences between males and females, specifically in terms of AD
neuropathology and cognitive decline. To advance the field, additional genetic effects must be discovered and
the underlying mechanisms of sex-specific pathways of injury must be examined. The objective of this project
is to identify and replicate genetic effects that act in a sex-specific manner to drive the neuropathological
presentation and clinical progression of AD. The present proposal will advance our understanding of sex-
specific genetic contributors to AD endophenotypes by leveraging data from 30 studies of aging and AD
(n=33,740) to assess genetic associations with AD neuropathology and cognitive decline. The outcome of this
project will highlight new candidate pathways and begin the process of characterizing the mechanisms by
which genetic variation among males and females affects the risk and clinical symptoms of AD. The sex-
specific pathways identified will offer therapeutic targets and help move the field towards personalized
interventions that consider an individual’s sex and neuropathological presentation.

## Key facts

- **NIH application ID:** 10862777
- **Project number:** 5R01AG073439-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Logan C Dumitrescu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $780,953
- **Award type:** 5
- **Project period:** 2021-09-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10862777

## Citation

> US National Institutes of Health, RePORTER application 10862777, Sex-Specific Genetic Drivers of Alzheimer's Disease Endophenotypes (5R01AG073439-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10862777. Licensed CC0.

---

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