Fully automated measurement of plasma Aβ42/40 and p-tau181: Analytical robustness and concordance with cerebrospinal fluid profile along the Alzheimer's disease continuum in two independent cohorts.

INTRODUCTION

For routine clinical implementation of Alzheimer's disease (AD) plasma biomarkers, fully automated random-access platforms are crucial to ensure reproducible measurements. We aimed to perform an analytical validation and to establish cutoffs for AD plasma biomarkers measured with Lumipulse.

METHODS

Two cohorts were included. UNIPG: n = 450 paired cerebrospinal fluid (CSF)/plasma samples from subjects along the AD-continuum, subjects affected by other neurodegenerative diseases, and controls with known CSF profile; AMS: n = 40 plasma samples from AD and n = 40 controls. Plasma amyloid β (Aβ)42, Aβ40, and p-tau181 were measured with Lumipulse. We evaluated analytical and diagnostic performance.

RESULTS

Lumipulse assays showed high analytical performance. Plasma p-tau181 levels accurately reflected CSF A+/T+ profile in AD-dementia and mild cognitive impairment (MCI)-AD, but not in asymptomatic-AD. Plasma and CSF Aβ42/40 values were concordant across clinical AD stages. Cutoffs and probability-based models performed satisfactorily in both cohorts.

DISCUSSION: The identified cutoffs and probability-based models represent a significant step toward plasma AD molecular diagnosis.