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

• Published in: Nature medicine Vol. 31; no. 6; pp. 2036 - 2043
• Main Authors: Palmqvist, Sebastian, Warmenhoven, Noëlle, Anastasi, Federica, Pilotto, Andrea, Janelidze, Shorena, Tideman, Pontus, Stomrud, Erik, Mattsson-Carlgren, Niklas, Smith, Ruben, Ossenkoppele, Rik, Tan, Kübra, Dittrich, Anna, Skoog, Ingmar, Zetterberg, Henrik, Quaresima, Virginia, Tolassi, Chiara, Höglund, Kina, Brugnoni, Duilio, Puig-Pijoan, Albert, Fernández-Lebrero, Aida, Contador, José, Padovani, Alessandro, Monane, Mark, Verghese, Philip B., Braunstein, Joel B., Kern, Silke, Blennow, Kaj, Ashton, Nicholas J., Suárez-Calvet, Marc, Hansson, Oskar
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.06.2025; Nature Publishing Group
• Subjects: 692/53/2421; 692/699/375/132/1283; Accuracy; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Apolipoprotein E; Automation; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Biomedical and Life Sciences; Biomedicine; Blood; Cancer Research; Cerebrospinal fluid; Cohort Studies; Diabetes mellitus; Female; Genotypes; Humans; Immunoassay; Infectious Diseases; Kidney diseases; Male; Metabolic Diseases; Middle Aged; Molecular Medicine; Neurodegenerative diseases; Neurosciences; Neurovetenskaper; Pathology; Peptide Fragments - blood; Peptide Fragments - cerebrospinal fluid; Phosphorylation; Plasma; Primary care; Primary Health Care; Secondary Care; Spectrometry; Subpopulations; Sweden; tau Proteins - blood; Sweden
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/s41591-025-03622-w

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. Among 1,767 patients in 5 centers, a fully automated blood test showed high accuracy for Alzheimer’s pathology in secondary and primary care using a predefined cutoff.