pTau217 in Admixed South American Populations: Implications for Alzheimer’s Disease Diagnosis in Brazil and Argentina

Plasma pTau217 is a leading biomarker for Alzheimer’s disease (AD), but evidence from low- and middle-income countries (LMICs) remains limited. We evaluated its diagnostic performance in two memory-clinic cohorts from Brazil (Cog-Aging-Study, n = 353) and Argentina (GeNED.ar, n = 134), both genetically admixed. Using data-driven mixture modelling with single- and two-cut-off approaches, we assessed concordance with clinical diagnosis and, in Cog-Aging-Study-Brazil, CSF-defined amyloid pathology. In Cog-Aging-Study-Brazil, pTau217 and pTau217/Aβ42 with two-cut-off strategies accurately predicted amyloid positivity and showed high concordance with clinical AD diagnosis. In GeNED.ar-Argentina, both biomarkers similarly aligned with clinical diagnosis. APOE-ε4 and lower BMI or eGFR were associated with higher pTau217 in Cog-Aging-Study-Brazil, while education additionally influenced biomarker levels in GeNED.ar-Argentina. African ancestry modified APOE effect on CSF but not plasma biomarkers. These findings show that pTau217-based biomarkers show good performance in admixed South American populations and support their implementation in LMICs with limited access to CSF and PET.