Comparison of the analytical and clinical performance of three immunoassay platforms for plasma glial fibrillary acidic protein in Alzheimer’s disease

OBJECTIVES: This study aimed to compare the analytical and clinical performance of plasma glial fibrillary acidic protein (GFAP) across three immunoassay platforms. METHODS: Plasma GFAP was measured on three immunoassay platforms (Simoa HD-X, Maccura i1000, MS-Fast Pro 160) in 302 participants from the Peking Union Medical College Hospital dementia cohort (139 Alzheimer's disease dementia [ADD], 116 non-AD dementia [NADD]). Inter-platform agreement was assessed using Passing-Bablok regression, Bland-Altman analysis, and Spearman correlation. ROC analyses and multimarker models on the Simoa platform were used to evaluate GFAP, NfL, a core plasma panel (Aβ1-42, p-tau181, p-tau217), and their combinations. RESULTS: Plasma GFAP levels were significantly higher in ADD than in NADD across all three platforms. Inter-platform correlations were strong (Spearman's r=0.874-0.932), but Passing-Bablok regression showed substantial proportional bias and systematically higher concentrations on the Simoa platform. ROC-based discrimination between ADD and NADD was comparable across platforms (AUC 0.732-0.740), whereas assay-specific optimal cut-offs differed markedly. On the Simoa platform, GFAP alone achieved an AUC of 0.731. The core plasma panel (Aβ1-42, p-tau181, p-tau217) achieved an AUC of 0.898, which increased to 0.924 after adding GFAP and NfL. CONCLUSIONS: This study provides a comparison of plasma GFAP measurements across three immunoassay platforms, revealing strong correlations but substantial differences in absolute values and decision cut-offs. The clinical analyses show that similar discriminative performance can coexist with markedly different platform-specific cut-offs, underscoring the need for platform-specific cut-offs and further harmonization of GFAP measurements.