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Blood-based AT(N) biomarkers for Alzheimer's disease and frontotemporal lobar degeneration in Latin America

Caviedes A, Cabral-Miranda F, Orellana P, Hernández H, Henríquez F, Gonzalez-Gomez R, Pizarro M, Migeot J, Ochoa-Rosales C, Gonzalez-Silva C, Marin-Diaz N, Coronel-Oliveros C, Santamaría-García H, Carmona D, García AM, Slachevsky A, Singleton A, Qi AY, Lawlor B, Miller B, Dhooge C, Pantazis C, Udeh-Momoh CT, Aguillón D, Matallana DL, Zimmer ER, Resende EPF, Farina FR, Cabello F, Lopera F, Zetterberg H, Avila-Funes JA, Acosta-Uribe J, Possin KL, Kosik KS, Hu K, Takada LT, de Oliveira MO, Maito MA, Suárez-Calvet M, Godoy ME, Behrens MI, Parra MA, Del Campo M, Bruno M, Gelvez N, Pozo-Castro N, Cochran JN, Custodio N, Ortega R, Santibanez R, de la Cruz R, Montesinos R, McDonagh S, Bandres-Ciga S, Javandel S, Brucki SMD, Pina-Escudero SD, Valcour V, Li Z, Yokoyama JS, Ibañez A, Duran-Aniotz C;

Resum

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.

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Referència

Caviedes A, Cabral-Miranda F, Orellana P, Hernández H, Henríquez F, Gonzalez-Gomez R, Pizarro M, Migeot J, Ochoa-Rosales C, Gonzalez-Silva C, Marin-Diaz N, Coronel-Oliveros C, Santamaría-García H, Carmona D, García AM, Slachevsky A, Singleton A, Qi AY, Lawlor B, Miller B, Dhooge C, Pantazis C, Udeh-Momoh CT, Aguillón D, Matallana DL, Zimmer ER, Resende EPF, Farina FR, Cabello F, Lopera F, Zetterberg H, Avila-Funes JA, Acosta-Uribe J, Possin KL, Kosik KS, Hu K, Takada LT, de Oliveira MO, Maito MA, Suárez-Calvet M, Godoy ME, Behrens MI, Parra MA, Del Campo M, Bruno M, Gelvez N, Pozo-Castro N, Cochran JN, Custodio N, Ortega R, Santibanez R, de la Cruz R, Montesinos R, McDonagh S, Bandres-Ciga S, Javandel S, Brucki SMD, Pina-Escudero SD, Valcour V, Li Z, Yokoyama JS, Ibañez A, Duran-Aniotz C; Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat). Blood-based AT(N) biomarkers for Alzheimer's disease and frontotemporal lobar degeneration in Latin America. Nat Aging. 2026 Feb;6(2):430-444. doi: 10.1038/s43587-025-01061-3. Epub 2026 Feb 13. PMID: 41688826.