# Genetic Contributions to Alzheimer’s Disease and Frontotemporal Dementia in Admixed Latin American Populations

## TL;DR

This study explores genetic factors contributing to Alzheimer’s and frontotemporal dementia in Latin American populations with mixed ancestry.

## Contribution

The study is the first large-scale genetic analysis of Alzheimer’s and frontotemporal dementia in admixed Latin American populations.

## Key findings

- Participants showed a mix of American, African, European, and in some cases East Asian ancestry.
- Seventeen pathogenic variants and a C9orf72 expansion were identified, along with 44 variants of uncertain significance.
- Seventy families exhibited autosomal dominant inheritance patterns for Alzheimer’s or frontotemporal dementia.

## Abstract

Latin America’s diverse genetic landscape provides a unique opportunity to
study Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The Multi-Partner
Consortium to Expand Dementia Research in Latin America (ReDLat) recruited 2,162
participants with AD, FTD, or as healthy controls from six countries: Argentina, Brazil,
Chile, Colombia, Mexico, and Peru. Participants underwent genomic sequencing and
population structure analyses were conducted using Principal Component Analysis and
ADMIXTURE. The study revealed a predominant mix of American, African, and European
ancestries, with an additional East Asian component in Brazil. Variant curation identified
17 pathogenic variants, pathogenic C9orf72 expansion, and 44 variants of
uncertain significance. Seventy families showed autosomal dominant inheritance, with 48
affected by AD and 22 by FTD. This represents the first large-scale genetic study of AD
and FTD in Latin America, highlighting the need to consider diverse ancestries, social
determinants of health, and cultural factors when assessing genetic risk for
neurodegenerative diseases.