Blood-based AT(N) biomarkers for Alzheimer's disease and frontotemporal lobar degeneration in Latin America.
| Title: | Blood-based AT(N) biomarkers for Alzheimer's disease and frontotemporal lobar degeneration in Latin America. |
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| Authors: | Caviedes A; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Cabral-Miranda F; Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.; Orellana P; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile.; Hernández H; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Henríquez F; Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Chile.; Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department - Institute of Biomedical Sciences (ICBM), Neuroscience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Santiago, Chile.; Laboratory for Cognitive and Evolutionary Neuroscience (LaNCE), Department of Psychiatry, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.; Gonzalez-Gomez R; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Neurology and Neurosurgery Department, Montreal Neurological Institute, Montreal, Québec, Canada.; Pizarro M; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile.; Migeot J; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Ochoa-Rosales C; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.; Gonzalez-Silva C; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Marin-Diaz N; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Center for Social and Cognitive Neuroscience (CSCN), School of Psychology, Universidad Adolfo Ibanez, Santiago, Chile.; Coronel-Oliveros C; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Santamaría-García H; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Pontificia Universidad Javeriana, Bogotá, Colombia.; Centro de Memoria y Cognición Intellectus, Hospital Universitario San Ignacio, Bogotá, Colombia.; Carmona D; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; García AM; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina.; Departamento de Lingüística y Literatura, Facultad de Humanidades, Universidad de Santiago de Chile, Santiago, Chile.; Slachevsky A; Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Chile.; Neuropsychology and Clinical Neuroscience Laboratory (LANNEC), Physiopathology Department - Institute of Biomedical Sciences (ICBM), Neuroscience and East Neuroscience Departments, Faculty of Medicine, University of Chile, Santiago, Chile.; Memory and Neuropsychiatric Center (CMYN) Neurology Department, Hospital del Salvador and Faculty of Medicine, Universidad de Chile, Santiago, Chile.; Departamento de Neurología y Psiquiatría, Clínica Semana-Universidad del Desarrollo, Santiago, Chile.; Singleton A; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.; Qi AY; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.; Lawlor B; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Miller B; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Dhooge C; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina.; Pantazis C; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.; Udeh-Momoh CT; School of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.; Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.; Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK.; Aguillón D; Grupo de Neurociencias de Antioquia (GNA), Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.; Matallana DL; Instituto de Genética Humana. Facultad de Medicina. Pontificia Universidad Javeriana, Bogotá, Colombia.; Departamento de Salud Mental, Hospital Universitario Fundación Santa Fe, Bogotá, Colombia.; Instituto de Envejecimiento, Pontificia Universidad Javeriana, Bogotá, Colombia.; Zimmer ER; Department of Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.; Graduate Program in Biological Sciences: Biochemistry (PPGBioq) and Pharmacology and Therapeutics (PPGFT), UFRGS, Porto Alegre, Brazil.; McGill University, Montreal, Québec, Canada.; Brain Institute of Rio Grande do Sul, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil.; Hospital Moinhos de Vento, Porto Alegre, Brazil.; Resende EPF; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.; Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Brazil.; Farina FR; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Pritzker School of Medicine, The University of Chicago, Chicago, IL, USA.; Cabello F; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Lopera F; Grupo de Neurociencias de Antioquia (GNA), Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.; Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.; UK Dementia Research Institute at UCL, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.; Avila-Funes JA; Dirección de Enseñanza. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.; INSERM, Bordeaux Population Health Research Center, UMR 1219, University of Bordeaux, Bordeaux, France.; Acosta-Uribe J; Grupo de Neurociencias de Antioquia (GNA), Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.; Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Possin KL; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Kosik KS; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.; Hu K; Medical Biodynamics Center, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Division of Sleep and Circadian Disorders, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.; Takada LT; Hospital das Clínicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.; de Oliveira MO; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Hospital das Clínicas, University of Sao Paulo School of Medicine, Sao Paulo, Brazil.; Maito MA; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina.; Suárez-Calvet M; Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.; Hospital del Mar Research Institute, Barcelona, Spain.; Servei de Neurologia, Hospital del Mar, Barcelona, Spain.; Godoy ME; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina.; Behrens MI; Departamento de Neurología y Psiquiatría, Clínica Semana-Universidad del Desarrollo, Santiago, Chile.; Centro de Investigación Clínica Avanzada (CICA) Hospital Clínico Universidad de Chile. Dr Carlos Lorca Tobar 999, Independencia, Santiago, Chile.; Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile. Dr Carlos Lorca Tobar 999, Independencia, Santiago, Chile.; Departamento de Neurociencia, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.; Parra MA; School of Psychological Sciences and Health, University of Strathclyde, Glasgow, UK.; Del Campo M; Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.; Hospital del Mar Research Institute, Barcelona, Spain.; Departamento de Ciencias Farmacéuticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain.; Bruno M; Institute of Biomedical Sciences (ICBM), Universidad Católica de Cuyo, San Juan, Argentina.; National Council on Scientific and Technical Research (CONICET), Buenos Aires, Argentina.; Gelvez N; Instituto de Genética Humana. Facultad de Medicina. Pontificia Universidad Javeriana, Bogotá, Colombia.; Pozo-Castro N; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Departamento de Neurología y Neurocirugía Norte, Facultad de Medicina, Universidad de Chile, Santiago, Chile.; Hospital Clínico San Borja Arriarán, Santiago, Chile.; Cochran JN; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.; Custodio N; Unidad de diagnóstico de deterioro cognitivo y prevención de demencia, Instituto Peruano de Neurociencias, Lima, Perú.; Ortega R; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile.; Santibanez R; Neurology Department, Pontificia Universidad Católica de Chile, Santiago, Chile.; de la Cruz R; Faculty of Engineering and Sciences, Universidad Adolfo Ibáñez, Santiago, Chile.; Data Observatory Foundation, ANID Technology Center No. DO210001, Santiago, Chile.; Montesinos R; Unidad de diagnóstico de deterioro cognitivo y prevención de demencia, Instituto Peruano de Neurociencias, Lima, Perú.; Unidad de Investigación, Equilibria, Lima, Perú.; Universidad de San Martín de Porres, Facultad de Medicina, Centro de Investigación del Envejecimiento, Lima, Perú.; McDonagh S; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Bandres-Ciga S; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.; Javandel S; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Brucki SMD; Cognitive and Behavioral Neurology Unit, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.; Pina-Escudero SD; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland.; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Valcour V; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Li Z; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.; DataTecnica LLC, Washington, DC, USA.; Yokoyama JS; Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.; Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.; Ibañez A; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile. agustin.ibanez@gbhi.org.; Global Brain Health Institute (GBHI), University of California, San Francisco (UCSF), San Francisco, CA, USA. agustin.ibanez@gbhi.org.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland. agustin.ibanez@gbhi.org.; Cognitive Neuroscience Center (CNC), Universidad de San Andrés, Buenos Aires, Argentina. agustin.ibanez@gbhi.org.; Department of Biophysics, School of Medicine, Istanbul Medipol University, Istanbul, Turkey. agustin.ibanez@gbhi.org.; Duran-Aniotz C; Latin American Brain Health Institute (BrainLat), Universidad Adolfo Ibanez, Santiago, Chile. claudia.duran@uai.cl.; Global Brain Health Institute (GBHI), Trinity College Dublin (TCD), Dublin, Ireland. claudia.duran@uai.cl. |
| Corporate Authors: | Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) |
| Source: | Nature aging [Nat Aging] 2026 Feb; Vol. 6 (2), pp. 430-444. Date of Electronic Publication: 2026 Feb 13. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group US Country of Publication: United States NLM ID: 101773306 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2662-8465 (Electronic) Linking ISSN: 26628465 NLM ISO Abbreviation: Nat Aging Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [New York] : Nature Publishing Group US, [2021]- |
| MeSH Terms: | Alzheimer Disease*/blood ; Alzheimer Disease*/diagnosis ; Frontotemporal Lobar Degeneration*/blood ; Frontotemporal Lobar Degeneration*/diagnosis ; Biomarkers*/blood ; tau Proteins*/blood ; Amyloid beta-Peptides*/blood ; Neurofilament Proteins*/blood; Peptide Fragments/blood ; Humans ; Latin America ; Male ; Female ; Aged ; Middle Aged ; Cohort Studies ; Aged, 80 and over |
| Abstract: | Dementia diagnosis increasingly relies on blood-based biomarkers, yet their performance in diverse populations remains insufficiently characterized. Latin America, with substantial genetic and environmental heterogeneity, is particularly underrepresented in biomarker research. Here we show that plasma AT(N) biomarkers can distinguish Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) in a multinational Latin American cohort (N = 605). Aβ42/Aβ40 amyloid-β ratios were reduced and levels of phosphorylated tau (p-tau217, p-tau181) and neurofilament light chain (NfL) were elevated in both disorders, with NfL showing greater increases in FTLD. Classification models achieved receiver operating characteristic areas under the curve (ROC AUCs) of 83% for AD and 88% for FTLD. Meta-analyses confirmed consistency across countries, and these markers correlated with executive, memory and global cognitive impairment. Biomarker alterations combined with disease-specific neuroimaging patterns and cognitive measures further improved accuracy (ROC AUCs of 89% for AD and 95% for FTLD). These findings indicate that plasma AT(N) biomarkers, combined with neuroimaging and clinical assessments, can enhance dementia diagnosis across diverse Latin American populations.; (© 2026. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
| Competing Interests: | Competing interests: H.Z. has served on scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave; has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk and Roche; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). Not related to the current work, K.H. is the Honorary Lifetime Co-founder of iFutureLab Inc., serves on the scientific advisory board of the company and has received consulting fees from the company. Z.L.’s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the NIH to support open science research. S.M.D.B. has served on scientific advisory boards and/or as a consultant for Biogen, Lilly, Novo Nordisk and Roche and has received a research productivity grant from the National Council for Scientific and Technological Development (Ministry of Science and Technology−Brazil). M.S.-C. has received consultancy/speaker fees (paid to the institution) in the past 36 months from Almirall, Lilly, Quanterix, Novo Nordisk and Roche Diagnostics. He has received consultancy fees from or served on advisory boards (paid to the institution) of Lilly, Grifols, Novo Nordisk and Roche Diagnostics. He was granted a project and is a site investigator of a clinical trial (funded to the institution) by Roche Diagnostics. In-kind support for research (to the institution) was received from ADx Neurosciences, Alamar Biosciences, ALZpath, Avid Radiopharmaceuticals, Lilly, Fujirebio, Janssen Research & Development, Meso Scale Discovery and Roche Diagnostics. M.S.-C. did not receive any personal compensation from these organizations or any other for-profit organization. The other authors declare no competing interests. |
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| Grant Information: | R01 AG057234 United States AG NIA NIH HHS |
| Contributed Indexing: | Investigator: E de Paula França Resende; MO de Oliveira |
| Substance Nomenclature: | 0 (Biomarkers); 0 (tau Proteins); 0 (Amyloid beta-Peptides); 0 (Neurofilament Proteins); 0 (neurofilament protein L); 0 (Peptide Fragments) |
| Entry Date(s): | Date Created: 20260213 Date Completed: 20260220 Latest Revision: 20260520 |
| Update Code: | 20260520 |
| DOI: | 10.1038/s43587-025-01061-3 |
| PMID: | 41688826 |
| Database: | MEDLINE |
Journal Article