Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform

Global implementation of blood tests for Alzheimer's disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts in Malmö (Sweden, n = 337), Gothenburg (Sweden, n = 165), Barcelona (Spain, n = 487) and Brescia (Italy, n = 230), and a primary care cohort in Sweden (n = 548). Plasma p-tau217 was primarily measured using the fully automated, commercially available, Lumipulse immunoassay. The primary outcome was AD pathology defined as abnormal cerebrospinal fluid Aβ42:p-tau181. Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93-0.96. In secondary care, the accuracies were 89-91%, the positive predictive values 89-95% and the negative predictive values 77-90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%), but was unaffected by chronic kidney disease, diabetes, sex, APOE genotype or cognitive stage. Using a two-cutoff approach, accuracies increased to 92-94% in secondary and primary care, excluding 12-17% with intermediate results. Using the plasma p-tau217:Aβ42 ratio did not improve accuracy but reduced intermediate test results (≤10%). Compared with a high-performing mass-spectrometry-based assay for percentage p-tau217, accuracies were comparable in secondary care. However, percentage p-tau217 had higher accuracy in primary care and was unaffected by age. In conclusion, this fully automated p-tau217 test demonstrates high accuracy for identifying AD pathology. A two-cutoff approach might be necessary to optimize performance across diverse settings and subpopulations.

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Publication Details

Journal
Nature Medicine
Published
2025-04-09
DOI
https://doi.org/10.1038/s41591-025-03622-w
Citations
97
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
142.71

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article

Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform

Philip B. Verghese, Nicholas James Ashton, Aida Fernández‐Lebrero, Mark Monane et al.
97 citations
Nature Medicine
Dementia and Cognitive Impairment Research
142.71
article

Plasma phospho-tau217 for Alzheimer’s disease diagnosis in primary and secondary care using a fully automated platform

Philip B. Verghese, Nicholas James Ashton, Aida Fernández‐Lebrero, Mark Monane, José Contador, Andrea Pilotto, Sebastian Palmqvist, Rik Ossenkoppele, Erik Stomrud, Kaj Blennow, Pontus Tideman, Chiara Tolassi, Virginia Quaresima, Ruben Smith, Joel B. Braunstein, Niklas Mattsson, Oskar Hansson, Kina Höglund, Ingmar Gr. Skoog, Anna Dittrich, Federica Anastasi, Duilio Brugnoni, Silke Kern, Henrik Zetterberg, Shorena Janelidze, Marc Suárez‐Calvet, Albert Puig‐Pijoan, Alessandro Padovani, Noëlle Warmenhoven, Kübra Tan
article en
97 citations

Abstract

Global implementation of blood tests for Alzheimer's disease (AD) would be facilitated by easily scalable, cost-effective and accurate tests. In the present study, we evaluated plasma phospho-tau217 (p-tau217) using predefined biomarker cutoffs. The study included 1,767 participants with cognitive symptoms from 4 independent secondary care cohorts in Malmö (Sweden, n = 337), Gothenburg (Sweden, n = 165), Barcelona (Spain, n = 487) and Brescia (Italy, n = 230), and a primary care cohort in Sweden (n = 548). Plasma p-tau217 was primarily measured using the fully automated, commercially available, Lumipulse immunoassay. The primary outcome was AD pathology defined as abnormal cerebrospinal fluid Aβ42:p-tau181. Plasma p-tau217 detected AD pathology with areas under the receiver operating characteristic curves of 0.93-0.96. In secondary care, the accuracies were 89-91%, the positive predictive values 89-95% and the negative predictive values 77-90%. In primary care, the accuracy was 85%, the positive predictive values 82% and the negative predictive values 88%. Accuracy was lower in participants aged ≥80 years (83%), but was unaffected by chronic kidney disease, diabetes, sex, APOE genotype or cognitive stage. Using a two-cutoff approach, accuracies increased to 92-94% in secondary and primary care, excluding 12-17% with intermediate results. Using the plasma p-tau217:Aβ42 ratio did not improve accuracy but reduced intermediate test results (≤10%). Compared with a high-performing mass-spectrometry-based assay for percentage p-tau217, accuracies were comparable in secondary care. However, percentage p-tau217 had higher accuracy in primary care and was unaffected by age. In conclusion, this fully automated p-tau217 test demonstrates high accuracy for identifying AD pathology. A two-cutoff approach might be necessary to optimize performance across diverse settings and subpopulations.

Nature MedicineVol. 31(6)
Universitat Autònoma de Barcelona (ES), University of Wisconsin–Madison (US), Universitat Pompeu Fabra (ES), King's College London (GB), Lund University (SE), Sahlgrenska University Hospital (SE), Sorbonne Université (FR), C2N Diagnostics (United States) (US), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Pasqual Maragall Foundation (ES), Amsterdam Neuroscience (NL), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), Barcelonaβeta Brain Research Center (ES), Hospital Del Mar (ES), Skåne University Hospital (SE), Centre for Genomic Regulation (ES), Banner Sun Health Research Institute (US), National Hospital for Neurology and Neurosurgery (GB), Institut du Cerveau (FR), Banner Alzheimer’s Institute, University College London (GB), University of Brescia (IT), Vrije Universiteit Amsterdam (NL), University of Gothenburg (SE)
Alzheimer's Association, Hjärnfonden, Vetenskapsrådet, National Institute on Aging
Good health and well-being
Openalex Percentile: Top 0%
Dementia and Cognitive Impairment Research
142.71
DOIOpen Access PDFOpenAlex
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