Prospective evaluation of plasma pTau217 stability for the detection of Alzheimer’s disease in a tertiary memory clinic
Year: 2025
Type: article
Study design: Observational Study
Abstract: 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.
Source: Alzheimer s Research & Therapy
Authors: 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
Institutions: Universitat Autònoma de Barcelona, Hospital de Sant Pau, Institut de Recerca Sant Pau, Biomedical Research Networking Center on Neurodegenerative Diseases, Complejo Hospitalario Torrecárdenas, Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas, Centro de Investigación Biomédica en Red
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,290
Funders: Alzheimer's Association, BrightFocus Foundation, Fundació la Marató de TV3, Global Brain Health Institute, European Commission, Fondation Jérôme Lejeune, Generalitat de Catalunya, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Fundación Tatiana Pérez de Guzmán el Bueno, Universitat Autònoma de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, National Institutes of Health, Horizon 2020 Framework Programme, Instituto de Salud Carlos III, European Regional Development Fund, National Institute on Aging
Awards: G1075404386, Interacción de la inflamación del sistema nervioso periférico y central en la enfermedad de Alzheimer y el síndrome de Down, G1178615512, G1272707494, Aplicación de Tomografía de Array (AT) para el estudio sistemático a gran escala del daño sináptico en las demencias neurodegenerativas, G1320099462, Caracterización multimodal de las etapas prodrómicas del espectro Alzheimer-Lewy, G1374560632, G1386747760, G1529925128, Avanzando la clasificación de la demencia frontotemporal y la esclerosis lateral amiotrófica mediante neuroimagen microestructural y funcional, y biomarcadores sanguíneos de neurodegeneración y neuroinflamación, DS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's Disease, G1661993316, G1838929904, G1853423388, G1875208949, G2120928055, G2275683183, La estructura cerebral y el metabolismo en la enfermedad de Alzheimer preclínica. Interacciones entre nuevos y viejos biomarcadores, G2362306273, G25525475, G2579412745, G2628364946, G2677554862, G2681669101, G2832483826, G2940840415, Cambios Microestructurales en la Degeneración Lobular Frontotemporal: Implicaciones diagnósticas, Pronósticas y Etiológicas, G2979977643, G3012247180, G3288897321, G3329934726, G3342877126, G3470407348, G3559709381, G3560792936, Caracterización de la inflamación relacionada con amiloide: nuevos marcadores inflamatorios y su impacto en la macroestructural y microestructura cortical en la enfermedad de Alzheimer preclínica y prodrómica, G367498634, G382602068, G3836773625, Enfermedad de Alzheimer y síndrome de Down. Estudios multimodales de líquido cefalorraquídeo, resonancia magnética y PET de amiloide, G3918816321, Proteínas en sangre para la discriminación precoz de las demencias, G434337789, G4350665218, G4484208813, G4509608868, G4511376228, Estudio del trazador de tomografía por emisión de positrones (PET) para Tau [18F]THK-5351 en pacientes con diferentes Taupatías, G4605335268, G4619213163, G4653472004, G4937468798, Utilidad diagnóstica de Aß42 y Aß42/40 en LCR y plasma para detectar amiloidosis cerebral y correlación con marcadores subrogados de producción de ß-amiloide en enf. de Alzheimer, G5469507914, G56143381, G5639301631, G5734573469, G5895271072, Caracterización de la epilepsia y de los trastornos de sueño en la enfermedad de Alzheimer esporádica y asociada al síndrome de Down, G6018678441, G6049260834, Estudios longitudinales de RM magnética estructural, de difusión y funcional en la enfermedad de Alzheimer preclínica esporádica y asociada al síndrome de Down, G6283029999, G6417120356, G6459257618, G6471528877, G6614811405, G6669287471, Afasia primaria progresiva: Caracterización multimodal de los síntomas, fisiopatología y progresión., G6938930710, G7093738275, G7335027413, G7683027334, G8047729998, Estudio de biomarcadores bioquímicos y de imagen de angiopatía amiloide cerebral en el continuum de la enfermedad de Alzheimer esporádica y asociada al síndrome de Down, Multimodal Assessment of Brain Inflammatory Biomarkers in DS-associated AD, G8284279906, G8289202400, G8351306399, G8418255654, G8726820484, G8824911526, G8858395165, G886509187, G8947099571, G8960147499, G9000024916, G9000055663, G9000056086, G9000057846, G9000082888, G9000196586, G9000212820, G9000213421, G9000226257, G9000232015, G9000236700, G931469340, G968800864
OpenAlex ID: W4412042857