AT(N) Plasma Biomarkers in Alzheimer's Disease and Frontotemporal Lobar Degeneration across Latin America

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Parra, Mario A., Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), (2025) AT(N) Plasma Biomarkers in Alzheimer's Disease and Frontotemporal Lobar Degeneration across Latin America. Nature Aging. ISSN 2662-8465 (In Press)

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Abstract

Blood-based biomarkers hold promise for improving dementia diagnosis but remain poorly validated in diverse populations. While AT(N) biomarkers for Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) are widely used in high-income countries, their assessment in Latin America is limited, despite the region’s genetic diversity, lifestyle variability, and diagnostic challenges. This study addresses these gaps by evaluating plasma biomarkers (Aβ42/Aβ40 ratio, p-149 tau217, p-tau181, and NfL) in an international cohort spanning five Latin American countries (n=605). Aβ42/Aβ40 ratio was significantly reduced in AD and FTLD compared to cognitively normal CN) individuals. P-tau217 and p-tau181 were elevated in both AD and FTLD, with higher NfL levels in FTLD compared to AD. Meta-analyses confirmed these effects at the individual country level. In AD, higher p-tau217 and NfL levels were associated with impairments in executive function, memory, and global cognition. In FTLD, these markers correlated with executive and global cognition deficits. Machine learning models using AT(N) biomarkers achieved ROC-AUC of 83% for AD and 88% for FTLD. Biomarker alterations were linked to temporo-parietal and occipital changes in AD, and orbito-insular and anterior-temporal regions in FTLD. Integrating neuropsychological assessments and clinical neuroimaging with biomarkers improved classification accuracy (CN vs AD=89%, CN vs FTLD=95%, AD vs FTLD=72%). These findings highlight the utility of AT(N) biomarkers, when combined with clinical assessments, to enhance dementia diagnosis across diverse Latin American populations.

ORCID iDs

Parra, Mario A. ORCID logoORCID: https://orcid.org/0000-0002-2412-648X;
CORE (COnnecting REpositories)