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

Abstract

INTRODUCTIONFor 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.METHODSTwo 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.RESULTSLumipulse 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.DISCUSSIONThe identified cutoffs and probability‐based models represent a significant step toward plasma AD molecular diagnosis.

Plasma p-tau217 in Alzheimer’s disease: Lumipulse and ALZpath SIMOA head-to-head comparison

“…This is particularly important when considering the transition from research to clinical use of such assays. 21,27,28 While our study demonstrates high concordance between the Lumipulse and SIMOA techniques, further validation efforts are warranted to confirm the biological relevance of plasma p-tau217 as a reliable biomarker for Alzheimer’s disease in different patient populations and disease stages, even using different standard-of-truth methods.…”

Exploring the Aβ1-42 fibrillogenesis timeline by atomic force microscopy and surface enhanced Raman spectroscopy

“…AD is typically diagnosed in vivo when irreparable brain damage has occurred, while the definite diagnosis of AD can only be made post-mortem, upon the detection of the aforementioned aggregates through brain autopsy ( Bistaffa et al, 2020 ). Therefore, one of the primary goals of the research in this field is to develop a sensitive, reproducible and cost-effective approach for the identification of diagnostic biomarkers, particularly in the early phases of AD, when a diagnosis based on cognitive symptoms is more uncertain and therapeutic intervention could be more efficacious ( Jack et al, 2018 ; Bellomo et al, 2021 ; Bellomo et al, 2024 ).…”