# Whole Genome Sequencing and Admixture Analyses of Neuropathologic Traits in Diverse Cohorts in USA and Brazil

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 2023 · $3,671,787

## Abstract

ABSTRACT
Identifying molecular drivers of Alzheimer’s disease and related dementias (AD/ADRD) pathologies is an
urgent public health priority. This is especially important in persons of African Ancestry. The overall goal of
the proposed study is to identify genes and proteins that drive common AD/ADRD pathologic traits.
We previously used multi-level omics to identify molecular drivers of AD/ADRD pathologic traits in non-Latinx
whites. The proposed study, submitted in response to NOT-AG-18-053 will extend this work by leveraging an
unique, ongoing, diverse study being conducted in Sao Paulo, Brazil, called “Pathology, Alzheimer´s and
Related Dementias Study” (PARDoS) and five other diverse cohorts in the USA, with whole genome
sequencing (WGS) on more than 1350 diverse autopsied participants. PARDoS is prospectively generating
neuropathologic and clinical AD/ADRD traits, and DNA on admixed Brazilians of European and African, and to
a lesser extent Native Brazilian ancestry. The proposal has the following Aims.
Aim 1 will generate WGS on an additional 7650 persons in collaboration with the Alzheimer’s Disease
Sequencing Project (ADSP). Aim 2 will perform deep admixture mapping of known SNPs for Alzheimer’s
dementia, to determine their associations with AD/ADRD neuropathologic phenotypes in 6500 admixed
Brazilian brains followed generalization to 300 diverse brains from the USA, and discovery analyses for 5500
Brazilians followed by generalization to 2000 diverse samples in the USA. Aim 3 will computationally determine
telomere length (TL) and examine their association with AD/ADRD clinical and pathologic traits. An exploratory
analysis will examine for rare variant associations with AD/ADRD neuropathologic traits.
Aim 5 will examine the
association of mitochondrial DNA to AD/ADRD traits.

## Key facts

- **NIH application ID:** 10590405
- **Project number:** 1R01AG075927-01A1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** DAVID ALAN BENNETT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $3,671,787
- **Award type:** 1
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10590405

## Citation

> US National Institutes of Health, RePORTER application 10590405, Whole Genome Sequencing and Admixture Analyses of Neuropathologic Traits in Diverse Cohorts in USA and Brazil (1R01AG075927-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10590405. Licensed CC0.

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