Prospective evaluation of plasma pTau217 stability for the detection of Alzheimer’s disease in a tertiary memory clinic

• Published in: Alzheimer's research & therapy Vol. 17; no. 1; pp. 150 - 13
• Main Authors: Arranz, Javier, Ferrer, Rosa, Zhu, Nuole, Rubio-Guerra, Sara, Rodríguez-Baz, Íñigo, Arriola-Infante, José Enrique, Maure-Blesa, Lucía, Garcia-Castro, Jesús, Selma-González, Judit, Carmona-Iragui, María, Barroeta, Isabel, Illán-Gala, Ignacio, Santos-Santos, Miguel, Fortea, Juan, Lleó, Alberto, Tondo, Mireia, Alcolea, Daniel
• Format: Journal Article
• Language: English
• Published: London BioMed Central 05.07.2025; BioMed Central Ltd; BMC
• Subjects: Alzheimer; Alzheimer's disease; Amyloid; Biomarkers; Biomedical and Life Sciences; Biomedicine; Blood; Clinics; Diagnosis; Geriatric Psychiatry; Geriatrics/Gerontology; Health aspects; Measurement; Medical examination; Neurology; Neurosciences; Plasma; Quality management; Stability; Tau proteins; Spain; Plasma; Stability; Biomarkers; Tau; Amyloid; Alzheimer; Blood
• ISSN: 1758-9193; 1758-9193
• DOI: 10.1186/s13195-025-01779-7

Background Knowledge on the effect of analytical variability and storage conditions are essential for the successful implementation of plasma pTau 217 in prospective settings. Aims To investigate the performance of plasma pTau 217 , 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 pTau 217 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 pTau 217 fold-change of 4.5 × compared to A-. We found no differences in plasma pTau 217 concentrations between either short-term storage conditions. The overall coefficients of analytical variation ranged from 1.8% to 3.2%. Plasma pTau 217 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 pTau 217 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 pTau 217 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.