Browsing by Author "Cochran, Nicholas"

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    Biomarkers for dementia in Latin American countries: Gaps andopportunities
    (2023) Parra, Mario A.; Orellana, Paulina; León, Tomas; Victoria, Cabello G.; Henriquez, Fernando; Gomez, Rodrigo; Avalos, Constanza; Damian, Andres; Slachevsky Chonchol, Andrea; Ibañez, Agustin; Zetterberg, Henrik; Tijms, Betty M.; Yokoyama, Jennifer S.; Piña-Escudero, Stefanie D.; Cochran, Nicholas; Matallana, Diana L.; Acosta, Daisy; Allegri, Ricardo; Arias-Suáres, Bianca P.; Barra, Bernardo; Behrens, María Isabel; Brucki, Sonia M.D.; Busatto, Geraldo; Caramelli, Paulo; Castro-Suarez, Sheila; Contreras, Valeria; Custodio, Nilton; Dansilio, Sergio; De la Cruz-Puebla, Myriam; Cruz de Souza, Leonado; Díaz, Monica M.; Duque, Lissette; Farias, Gonzalo A.; Ferreira, Sergio T.; Magrath Guimet, Nahuel; Kmaid, Ana; Lira, David; Lopera, Francisco; Mar Meza, Beatriz; Miotto, Eliane C.
    Limited knowledge on dementia biomarkers in Latin American and Caribbean (LAC)countries remains a serious barrier. Here, we reported a survey to explore the ongo-ing work, needs, interests, potential barriers, and opportunities for future studiesrelated to biomarkers. The results show that neuroimaging is the most used biomarker(73%), followed by genetic studies (40%), peripheral fluids biomarkers (31%), and cere-brospinal fluid biomarkers (29%). Regarding barriers in LAC, lack of funding appears toundermine the implementation of biomarkers in clinical or research settings, followedby insufficient infrastructure and training. The survey revealed that despite the abovebarriers, the region holds a great potential to advance dementia biomarkers research.Considering the unique contributions that LAC could make to this growing field,we highlight the urgent need to expand biomarker research. These insights allowedus to propose an action plan that addresses the recommendations for a biomarkerframework recently proposed by regional experts.
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    Comprehensive Analysis of Genetic Contributions to Alzheimer’s Disease and Frontotemporal Dementia in Admixed Latin American Populations
    (2024) Acosta, Juliana; Pina, Stefanie; Cochran, Nicholas; Taylor, Jared; Warly, Caroline; Matallana, Diana; Tadao, Leonel; Bruno, Martin; Levine, Alexandra; George, Dawwod; Lopera, Francisco; Slachevsky Chonchol, Andrea; Behrens, María; Ávila, José; Zapata, Lina; Brusco, Luis; Custodio, Nilton; Ramos, Teresita; Bruna, Bárbara; Ponce, Daniela; Gelvez, Nancy; Lopez, Greizy; Gomez, Luisa; Buitrago, Carlos; Reyes, Pablo; Durón, Dafne; Pantazis, Caroline; Maito, Marcelo; Javandel, Shireen; Godoy, Maria; Bistue, Maria; Vitale, Dan; Nalls, Mike; Singleton, Andrew; Miller, Bruce; Ibáñez, Agustín; Kosik, Kenneth; Yokoyama, Jennifer; Montesinos, Rosa; França, Elisa de Paula; Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat)
    Background: 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

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