Blood biomarkers for Alzheimer disease across ethnoracial groups and healthcare settings: a systematic review and meta-analysis

Blood-based biomarkers could transform Alzheimer disease (AD) detection by enabling scalable, less invasive assessment of underlying pathology, yet their applicability across globally diverse populations remains uncertain. We systematically reviewed 168 publications comprising 139 independent cohorts from Asia, Europe, North America, South America, Africa and Oceania. Random-effects meta-analyses pooled log-transformed ratios of mean biomarker concentrations for AD versus cognitively unimpaired individuals, mild cognitive impairment versus cognitively unimpaired individuals, and amyloid-β PET-positive versus amyloid-β PET-negative individuals. p-tau217, p-tau181 and glial fibrillary acidic protein showed the largest and most consistent group differences. In clinically defined comparisons, p-tau181 separation in mild cognitive impairment was lower in predominantly Asian than White cohorts, whereas glial fibrillary acidic protein separation in AD was higher in predominantly Asian cohorts. No significant between-population differences were observed in amyloid-defined comparisons. These findings support leading blood biomarkers as globally relevant indicators of AD pathology, but rigorous harmonized validation is needed before thresholds can be translated into equitable clinical practice.