# US-South American Initiative for Genetic-Neural-Behavioral Interactions in Human Neurodegenerative Research

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $521,480

## Abstract

PROJECT SUMMARY/ABSTRACT
Although dementia has a global impact, efforts to address ensuing challenges have come mostly from high-
income countries (HICs). Whereas the prevalence and incidence of dementia appear to be stable or declining
in such countries, an alarmingly opposite tendency typifies South American countries (SAC). This scenario
proves even more challenging due to region-specific traits. First, the particular genetic and environmental
backgrounds of SAC limit the generalizability of key findings from HICs. Moreover, the greater genetic diversity
and impact of socioeconomic status (SES) of SAC remain markedly understudied. Of note, this is true of the
four largest SAC (Brazil, Argentina, Colombia, and Peru), representing over 75% of the region’s population. In
addition, SAC face a dearth of innovative, harmonized, and cross-regional studies on two of their most
prevalent neurodegenerative disorders: Alzheimer’s disease (AD) and frontotemporal dementia (FTD). It is
thus critical for SAC to join ongoing international efforts and develop a gold-standard approach for detecting
disease-specific alterations in a context of methodological, genetic, and socioeconomic heterogeneity. Against
this background, our long-term goal is to identify the unique genetic and SES factors that drive AD and FTD
presentation in SAC relative to the US. To this end, we will establish a cohort to test large samples from the
four abovementioned SAC, as well as the US (totaling > 3000 participants, including 1500 controls, 750 AD
patients, and 750 FTD patients). We will combine standardized clinical assessments with innovative analytical
techniques including multimodal machine learning to account for heterogeneity in these diverse populations.
By combining standardized genetic, neuroimaging, and behavioral (SES-cognitive) measures, we will test the
underlying hypothesis that there are unique risk factors for AD and FTD in SAC which do not prove significant
in US populations. More particularly, we will aim to (a) establish genetic risk to AD and FTD in diverse SAC
cohorts; (b) test whether patients from SAC and the US can be discriminated after accounting for how SES
affects cognitive and brain imaging signatures; and (c) determine genetic, cognitive, cerebral, and
socioeconomic factors that discriminate among SAC vs. US patients. Positive impacts of this work include a
better understanding of the genetic and socioeconomic factors driving neurocognitive manifestations of
dementia, and the identification of novel genetic targets for risk reduction and disease prevention in SAC. Our
large multimodal, cross-sectional study will enable clinical assessment of understudied patient groups, extend
and harmonize existing data sets, and prompt the development of novel measures and multimodal machine
learning protocols. More generally, by establishing a collaborative framework which capitalizes on unique
regional populations, our proposal can consolidate a SAC-based platform f...

## Key facts

- **NIH application ID:** 10239263
- **Project number:** 5R01AG057234-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Nilton Custodio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $521,480
- **Award type:** 5
- **Project period:** 2019-09-30 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239263

## Citation

> US National Institutes of Health, RePORTER application 10239263, US-South American Initiative for Genetic-Neural-Behavioral Interactions in Human Neurodegenerative Research (5R01AG057234-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239263. Licensed CC0.

---

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