Concordance between amyloid PET and CSF biomarkers in clinical setting: a cross-platform comparison and in-depth analysis of discordant cases

Abstract

Abstract Reliable detection of amyloid pathology is essential for Alzheimer’s disease (AD) diagnosis and treatment. We directly compared routine ELISA assays and the automated Lumipulse platform against quantitative amyloid PET in a real-world memory clinic cohort. In 153 participants, flutemetamol amyloid PET and CSF biomarkers were assessed across platforms. Concordance with PET and predictors of discordance were evaluated. PET visual reads and Centiloids showed near-perfect agreement (AUC = 0.99). The p-tau181/Aβ42 ratio achieved the highest concordance with PET (OPA 87% ELISA, 92% Lumipulse), while the Lumipulse Aβ42/40 ratio reached 93%. About 6% of participants showed consistent discordance between CSF and PET, associated with APOE ε4 and mixed or non-AD pathologies. Automated CSF assays align strongly with amyloid PET and support biomarker standardization. Persistent discrepancies between CSF and PET likely reflect underlying biological heterogeneity such as mixed or non-AD pathologies and APOE ε4 carriage.