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Publications

Journal Article Ppublish

PubMed: 40205199 DOI: 10.1038/s41591-025-03622-w

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

Nat Med 31(6):2036-2043

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

Affiliations

  • Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
  • Memory Clinic, Skåne University Hospital, Malmö, Sweden.
  • Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
  • Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.
  • Hospital del Mar Research Institute, Barcelona, Spain.
  • Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
  • Department of Continuity of Care and Frailty, Neurology Unit, ASST Spedali Civili Hospital, Brescia, Italy.
  • Neurobiorepository and Laboratory of advanced biological markers, University of Brescia and ASST Spedali Civili Hospital, Brescia, Italy.
  • Memory Clinic, Skåne University Hospital, Malmö, Sweden.
  • Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden.
  • Neurology, Vrije Universiteit Amsterdam, Alzheimer Center Amsterdam, Amsterdam, The Netherlands.
  • Amsterdam Neuroscience-Neurodegeneration, Vrijie Universiteit Amersterdam, Amsterdam, The Netherlands.
  • Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
  • Department of Neuropsychiatry, Region Västra Götaland, Sahlgrenska University Hospital, Mölndal, Sweden.
  • Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
  • Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, London, UK.
  • UK Dementia Research Institute at UCL, London, UK.
  • Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
  • Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • Residency Program in Clinical Pathology and Clinical Biochemistry, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  • Central Laboratory for Clinical Chemistry, ASST Spedali Civili Hospital, Brescia, Italy.
  • Brain Health Center, University of Brescia, Brescia, Italy.
  • Department of Clinical Genetics and Genomics, Center for Medical Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Servei de Neurologia, Hospital del Mar, Barcelona, Spain.
  • Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
  • Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
  • C2N Diagnostics LLC, St. Louis, MO, USA.
  • Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
  • Neuroscience Maurice Wohl Clinical Neuroscience Institute, King's College London, Institute of Psychiatry, London, UK.
  • Banner Alzheimer's Institute, Phoenix, AZ, USA.
  • Banner Sun Health Research Institute, Sun City, AZ, USA.
  • Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.

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.

MeSH

Alzheimer Disease, Molecular Biology, Secondary Care, Pathology, Diagnosis, Plasma

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