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. 2026;2(1):5.
doi: 10.1038/s44400-025-00025-z. Epub 2026 Jan 21.

Genetic contributions to Alzheimer's disease and frontotemporal dementia in admixed Latin American populations

Juliana Acosta-Uribe #  1   2 , Stefanie D Piña-Escudero #  3   4 , J Nicholas Cochran  5 , Jared W Taylor  5 , P Alejandra Castruita  4 , Caroline Jonson  4   6   7 , Erin A Barinaga  5 , Kevin Roberts  5 , Alexandra R Levine  2 , Dawwod S George  2 , José Alberto Ávila-Funes  8   9 , María I Behrens  10   11 , Martín A Bruno  12   13 , Luis I Brusco  14   15 , Nilton Custodio  16 , Claudia Durán-Aniotz  17 , Francisco Lopera  1 , Diana L Matallana  18   19   20 , Andrea Slachevsky  10   21   22   23 , Leonel T Takada  24 , Lina M Zapata-Restrepo  25   26 , Dafne E Durón-Reyes  8 , Elisa de Paula França Resende  3   27 , Luisa F Gómez  28 , Nancy Gelvez  28 , M Beatriz Bistue  12   13 , Maria E Godoy  17 , Marcelo A Maito  17 , Shireen Javandel  3   4 , Bruce L Miller  3   4 , Mike A Nalls  6   7 , Hampton Leonard  6   7 , Dan Vitale  6   7 , Sara Bandres-Ciga  7 , Mathew J Koretsky  6   7 , Andrew B Singleton  7   29 , Caroline B Pantazis  7 , Victor Valcour  3   4   30 , Agustin Ibañez  17   31 , Kenneth S Kosik  2 , Jennifer S Yokoyama  3   4   32 ; Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat)*
Collaborators, Affiliations

Genetic contributions to Alzheimer's disease and frontotemporal dementia in admixed Latin American populations

Juliana Acosta-Uribe et al. NPJ Dement. 2026.

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 2162 participants with AD, FTD, or 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, a 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.

Keywords: Cognitive ageing; Dementia; Neurodegenerative diseases; Population genetics; Rare variants.

PubMed Disclaimer

Conflict of interest statement

Competing interestsM.A.N. owns stock from Character Bio Inc. and Neuron23 Inc. K.S.K. and J.S.Y. are members of the scientific advisory board of the Epstein Family Alzheimer’s Research Collaboration. K.S.K. is a member of the board of directors of the Tau Consortium and consults with Expansion Therapeutics and ADRx Pharma. J.S.Y. is Editor-in-Chief for npj Dementia. J.S.Y. was not involved in the journal’s review of, or decisions related to, this paper.

Figures

Fig. 1
Fig. 1. Assembly of the ReDLat genomic dataset.
WES whole exome sequencing, WGS whole genome sequencing, SNP single-nucleotide polymorphism.
Fig. 2
Fig. 2. Principal component analysis (PCA) of the ReDLat dataset and individuals from the 1000 Genome project (1000GP).
Panels represent the main principal component (PC) comparisons. a, d, g: PC1 vs. PC2. b, e, h: PC1 vs. PC3. c, f, i PC2 vs. PC3. Different color schemes were used to differentiate sample origin. The 1000GP includes African (AFR), European (EUR), South Asian (SAS), East Asian (EAS) and Admixed American (AMR) individuals. ReDLat subcohorts include individuals from Argentina (ARG), Brazil (BRA), Chile (CHI), Colombia (COL), Mexico (MEX), and Peru (PER). Panels a, b, c show color-coded ReDLat cohort participants projected onto the 1000GP reference samples PCA (gray). ReDLat cohort genomes are colored according to their country of origin. d, e, f show the ReDLat cohort (magenta) plotted against the color-coded 1000GP subpopulations. Panels g, h, i show ReDLat cohort (magenta) overlaid on 1000GP cohort (gray).
Fig. 3
Fig. 3. Global ancestry proportions of the ReDLat cohort represented by ADMIXTURE Q values assuming 5 ancestral populations (K).
The 1000 Genomes project includes African (AFR): GWD Gambian in Western Divisions in the Gambia, LWK Luhya in Webuye, MSL Mende in Sierra Leone, YRI Yoruba in Ibadan, Nigeria, ACB African Caribbean in Barbados, ASW African Ancestry in the Southwest US. European (EUR): CEU Utah Residents (CEPH) with Northern and Western European Ancestry, FIN Finnish in Finland, GBR British in England and Scotland, IBS Iberian Population in Spain, TSI Tuscany in Italia. South Asian (SAS): BEB Bengali in Bangladesh, GHI Gujarati Indians in Houston, ITU Indian Telugu in the UK, PJL Punjabi in Lahore, STU Sri Lankan Tamil in the UK. East Asian (EAS): CDX Chinese Dai in Xishuangbanna, China, CHB Han Chinese in Beijing, CHS Han Chinese South, JPT Japanese, Kyushu, KHV Kinh Vietnamese. Admixed American (AMR): CLM Colombian from Medellin, PUR Puerto Rican from Puerto Rico. ReDLat subcohorts: ARG Argentina, BRA Brazil, CHI Chile, COL Colombia, MEX Mexico, PER Peru.
Fig. 4
Fig. 4
Cosegregation analysis of APOE ε4 and neurodegeneration in families with multiple affected individuals.
See this image and copyright information in PMC

Update of

  • Genetic Contributions to Alzheimer's Disease and Frontotemporal Dementia in Admixed Latin American Populations.
    Acosta-Uribe J, Piña Escudero SD, Cochran JN, Taylor JW, Castruita PA, Jonson C, Barinaga EA, Roberts K, Levine AR, George DS, ÁvilaFunes JA, Behrens MI, Bruno MA, Brusco LI, Custodio N, Duran-Aniotz C, Lopera F, Matallana DL, Slachevsky A, Takada LT, Zapata-Restrepo LM, Durón-Reyes DE, de Paula França Resende E, Gelvez N, Godoy ME, Maito MA, Javandel S, Miller BL, Nalls MA, Leonard H, Vitale D, Bandres-Ciga S, Koretsky MJ, Singleton AB, Pantazis CB, Valcour V, Ibañez A, Kosik KS, Yokoyama JS; Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat). Acosta-Uribe J, et al. medRxiv [Preprint]. 2024 Nov 1:2024.10.29.24315197. doi: 10.1101/2024.10.29.24315197. medRxiv. 2024. Update in: NPJ Dement. 2026;2(1):5. doi: 10.1038/s44400-025-00025-z. PMID: 39574875 Free PMC article. Updated. Preprint.
  • Genetic Contributions to Alzheimer's Disease and Frontotemporal Dementia in Admixed Latin American Populations.
    Acosta-Uribe J, Escudero SDP, Cochran JN, Taylor JW, Castruita PA, Jonson C, Barinaga EA, Roberts K, Levine AR, George DS, Avila-Funes JA, Behrens MI, Bruno MA, Brusco LI, Custodio N, Duran-Aniotz C, Lopera F, Matallana DL, Slachevsky A, Takada LT, Zapata-Restrepo LM, Durón-Reyes DE, de Paula França Resende E, Gómez LF, Gelvez N, Bistue MB, Godoy ME, Maito MA, Javandel S, Miller BL, Nalls MA, Leonard H, Vitale D, Bandres-Ciga S, Koretsky MJ, Singleton AB, Pantazis CB, Valcour V, Ibañez A, Kosik KS, Yokoyama JS; Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat). Acosta-Uribe J, et al. Res Sq [Preprint]. 2025 May 6:rs.3.rs-5462510. doi: 10.21203/rs.3.rs-5462510/v1. Res Sq. 2025. Update in: NPJ Dement. 2026;2(1):5. doi: 10.1038/s44400-025-00025-z. PMID: 40386425 Free PMC article. Updated. Preprint.

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