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Comprehensive Analysis of Genetic Contributions to Alzheimer’s Disease and Frontotemporal Dementia in Admixed Latin American Populations

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dc.contributor.authorAcosta, Juliana
dc.contributor.authorPina, Stefanie
dc.contributor.authorCochran, Nicholas
dc.contributor.authorTaylor, Jared
dc.contributor.authorWarly, Caroline
dc.contributor.authorMatallana, Diana
dc.contributor.authorTadao, Leonel
dc.contributor.authorBruno, Martin
dc.contributor.authorLevine, Alexandra
dc.contributor.authorGeorge, Dawwod
dc.contributor.authorLopera, Francisco
dc.contributor.authorSlachevsky Chonchol, Andrea
dc.contributor.authorBehrens, María
dc.contributor.authorÁvila, José
dc.contributor.authorZapata, Lina
dc.contributor.authorBrusco, Luis
dc.contributor.authorCustodio, Nilton
dc.contributor.authorRamos, Teresita
dc.contributor.authorBruna, Bárbara
dc.contributor.authorPonce, Daniela
dc.contributor.authorGelvez, Nancy
dc.contributor.authorLopez, Greizy
dc.contributor.authorGomez, Luisa
dc.contributor.authorBuitrago, Carlos
dc.contributor.authorReyes, Pablo
dc.contributor.authorDurón, Dafne
dc.contributor.authorPantazis, Caroline
dc.contributor.authorMaito, Marcelo
dc.contributor.authorJavandel, Shireen
dc.contributor.authorGodoy, Maria
dc.contributor.authorBistue, Maria
dc.contributor.authorVitale, Dan
dc.contributor.authorNalls, Mike
dc.contributor.authorSingleton, Andrew
dc.contributor.authorMiller, Bruce
dc.contributor.authorIbáñez, Agustín
dc.contributor.authorKosik, Kenneth
dc.contributor.authorYokoyama, Jennifer
dc.contributor.authorMontesinos, Rosa
dc.contributor.authorFrança, Elisa de Paula
dc.contributor.authorMulti-Partner Consortium to Expand Dementia Research in Latin America (ReDLat)
dc.date.accessioned2025-08-25T18:14:31Z
dc.date.available2025-08-25T18:14:31Z
dc.date.issued2024
dc.description.abstractBackground: Most research initiatives have emerged from high-income countries (HIC), leaving a gap in understanding the disease’s genetic basis in diverse populations like those in Latin American countries (LAC). ReDLat tackles this gap, focusing on LAC’s unique genetics and socioeconomic factors to identify specific Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) risk factors in Mexico, Colombia, Peru, Chile, Argentina, and Brazil. Method: We employed a comprehensive genetic analysis approach, integrating Whole Genome Sequencing (WGS), Exome Sequencing, and SNP arrays to understand the cohort’s unique genetic architecture.We conducted ancestry analysis and searched for disease-causing variants with mendelian inheritance, genome-wide association studies (GWAS), rare variant enrichment, and evaluation of Polygenic Risk Scores (PRS). Results: We recruited and genotyped an initial cohort of 1046 participants with AD, 423 with FTD, and 855 healthy controls (HC) between 2020 and 2023. Analysis is ongoing, and we expect to sequence ∼600 additional samples in the coming months. Ancestry analysis revealed tri-continental admixture, except for Brazil, which showed an additional Asian component (Figure 1). Top candidate gene rare variant enrichment associations (SKAT p < 0.05) were TREM2 for FTD and ABCA7 and ABCA1 for AD. GWAS identified a robust association with the APOE locus on chromosome 19 in AD vs. HC.. We tested an AD PRS developed in European populations by Bellenguez et al (2020). on our cohort using 83 single-nucleotide polymorphisms.. The PRS modestly distinguishes between all patients and HC (p = 2.4 × 10ˆ-12), AD vs. HC (p = 2.2 × 10ˆ-12), and even FTD vs. HC (p = 4.3 × 10ˆ-5), albeit with modest separation between groups, as expected for its application in a genetically admixed population. Conclusion: Our findings represent a pivotal step in understanding the genetic landscape of AD and FTD in admixed populations. They underscore the importance of including diverse populations in genetic research, paving the way for future studies. These findings have the potential to inform more personalized approaches to the diagnosis and treatment of neurodegenerative diseases in diverse global populations, as well as identify novel targets for therapeutic development
dc.description.versionVersión Publicada
dc.identifier.citationAcosta‐Uribe, J., Escudero, S. D. P., Cochran, J. N., Taylor, J. W., Solsberg, C. W., Matallana, D., Takada, L. T., Bruno, M. A., Levine, A. R., George, D. S., Lopera, F., Slachevsky Chonchol, A., Behrens, M. I., Funes, J. a. Á., Zapata‐Restrepo, L. M., Brusco, L. I., Custodio, N., Franco, T. R., Bruna, B., De Paula França Resende, E. (2024). Comprehensive analysis of genetic contributions to Alzheimer’s disease and frontotemporal dementia in admixed Latin American populations. Alzheimer´s & Dementia, 20(S1). https://doi.org/10.1002/alz.093055
dc.identifier.doihttps://doi.org/10.1002/alz.093055
dc.identifier.urihttps://hdl.handle.net/11447/10222
dc.language.isoen
dc.titleComprehensive Analysis of Genetic Contributions to Alzheimer’s Disease and Frontotemporal Dementia in Admixed Latin American Populations
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceAlzheimer´s & Dementia
dspace.entity.typePublication
relation.isAuthorOfPublicatione25c3d3e-63b5-4e04-951a-12a4989aa772
relation.isAuthorOfPublication.latestForDiscoverye25c3d3e-63b5-4e04-951a-12a4989aa772

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