Javier Arranz, Rosa Ferrer, Nuole Zhu, Sara Rubio-Guerra, Íñigo Rodríguez-Baz, José Enrique Arriola-Infante, Lucía Maure-Blesa, Jesús Garcia-Castro, Judit Selma-González, María Carmona-Iragui, Isabel Barroeta, Ignacio Illán-Gala, Miguel Santos-Santos, Juan Fortea, Alberto Lleó, Mireia Tondo, Daniel Alcolea
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引用次数: 0
Abstract
Background: Knowledge on the effect of analytical variability and storage conditions are essential for the successful implementation of plasma pTau217 in prospective settings.
Aims: To investigate the performance of plasma pTau217, measured in consecutive samples with LUMIPULSE, for detecting Alzheimer's disease in a prospective memory clinic setting, along with evaluating its pre-analytical and analytical stability.
Methods: We prospectively measured pTau217 using the LUMIPULSE automated platform in consecutive patient plasma samples collected between May and November 2024 at the Sant Pau Memory Unit (Barcelona). A subset of participants also underwent paired lumbar puncture for CSF AD biomarkers. We compared biomarker concentrations under different short-term storage conditions (4ºC vs -20ºC) and different protocol pipelines, and assessed lot-to-lot variability. In the subset with available CSF biomarkers, logistic regression was used to evaluate the association between plasma pTau217 and the likelihood of a positive (A +) or a negative (A-) CSF amyloid status. Using ROC analysis, in this prospective cohort we evaluated the accuracy of previously established thresholds derived from historical samples.
Results: We included 280 participants, divided into two groups: those with (n = 109) and without CSF data (n = 171). Among the subset with CSF, 48% were A + , with a plasma pTau217 fold-change of 4.5 × compared to A-. We found no differences in plasma pTau217 concentrations between either short-term storage conditions. The overall coefficients of analytical variation ranged from 1.8% to 3.2%. Plasma pTau217 concentrations were slightly higher in paired samples of the clinical protocol. Following a two-threshold approach, the need of confirmatory tests (grey zones) after measuring plasma pTau217 ranged between 45.9% and 18.3% using our previously reported strict or lenient cutoffs (overall accuracy 96.6% and 92.1%, respectively).
Conclusions: The robust stability and low lot-to-lot variability of plasma pTau217 measurement in an automated platform result in high diagnostic performance of this biomarker in the prospective evaluation of patients in a memory clinic setting. These findings support its implementation into clinical routine, offering clinicians an accessible biomarker for AD diagnosis.
期刊介绍:
Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.