Plasma p-tau217 as a biomarker of Alzheimer’s disease pathology in individuals with Down syndrome

Diagnosing Alzheimer's disease (AD) in adults with Down syndrome (DS), a population with a high genetically determined risk of AD, remains challenging. In this large observational study including n = 2329 samples from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and euploid controls from the Sant Pau Initiative on Neurodegeneration (SPIN) with and without symptomatic AD, we investigate if the strong diagnostic performance of plasma p-tau217 observed in sporadic AD extends to the DS population. Plasma p-tau217 discriminated cognitively stable individuals with DS from those with AD dementia with an AUC of 0.96 (95% CI, 0.95-0.97), and from those with prodromal AD with an AUC of 0.90 (95% CI, 0.87-0.92). Amyloid β (Aβ) positive and Aβ negative individuals with DS were distinguished with an AUC of 0.95 (95% CI, 0.92-0.99). In this study, we demonstrate that plasma p-tau217 is highly accurate in detecting amyloid β positivity and predicting clinical progression in individuals with DS, outperforming other plasma biomarkers. These findings support its use as a reliable, noninvasive tool for early AD detection and management in individuals with DS.

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Publication Details

Journal
Nature Communications
Published
2025-11-10
DOI
https://doi.org/10.1038/s41467-025-65882-x
Primary Topic
Down syndrome and intellectual disability research
Type
article
Field-Weighted Citation Impact
0.00

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article

Plasma p-tau217 as a biomarker of Alzheimer’s disease pathology in individuals with Down syndrome

Guglielmo Di Molfetta, Nicholas James Ashton, Juan Fortea, Hanna Huber et al.
Nature Communications
Down syndrome and intellectual disability research
article

Plasma p-tau217 as a biomarker of Alzheimer’s disease pathology in individuals with Down syndrome

Guglielmo Di Molfetta, Nicholas James Ashton, Juan Fortea, Hanna Huber, Alberto Lleó, Laura del Hoyo Soriano, Bessy Benejam, Kaj Blennow, Íñigo Rodríguez‐Baz, Jon Infante, Laura Videla, Burak Arslan, Antoine Leuzy, Ignacio Illán‐Gala, Isabel Barroeta, Laia Montoliu‐Gaya, María Carmona‐Iragui, Lucía Maure-Blesa, Henrik Zetterberg, Alexandre Bejanin, Daniel Andres Alcolea, Javier Arranz, Oscar Kittel
article en

Abstract

Diagnosing Alzheimer's disease (AD) in adults with Down syndrome (DS), a population with a high genetically determined risk of AD, remains challenging. In this large observational study including n = 2329 samples from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and euploid controls from the Sant Pau Initiative on Neurodegeneration (SPIN) with and without symptomatic AD, we investigate if the strong diagnostic performance of plasma p-tau217 observed in sporadic AD extends to the DS population. Plasma p-tau217 discriminated cognitively stable individuals with DS from those with AD dementia with an AUC of 0.96 (95% CI, 0.95-0.97), and from those with prodromal AD with an AUC of 0.90 (95% CI, 0.87-0.92). Amyloid β (Aβ) positive and Aβ negative individuals with DS were distinguished with an AUC of 0.95 (95% CI, 0.92-0.99). In this study, we demonstrate that plasma p-tau217 is highly accurate in detecting amyloid β positivity and predicting clinical progression in individuals with DS, outperforming other plasma biomarkers. These findings support its use as a reliable, noninvasive tool for early AD detection and management in individuals with DS.

Nature CommunicationsVol. 16(1)
Universitat Autònoma de Barcelona (ES), University of Science and Technology of China (CN), University of Wisconsin–Madison (US), Sahlgrenska University Hospital (SE), German Center for Neurodegenerative Diseases (DE), Hospital de Sant Pau (ES), Banner Health (US), Sorbonne Université (FR), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), Banner Sun Health Research Institute (US), Complejo Hospitalario Torrecárdenas (ES), National Hospital for Neurology and Neurosurgery (GB), Institut du Cerveau (FR), Banner Alzheimer’s Institute, University College London (GB), University of Gothenburg (SE)
Alzheimer's Association, BrightFocus Foundation, European Commission, Fondation Jérôme Lejeune, Generalitat de Catalunya, Hjärnfonden, Vetenskapsrådet, Göteborgs Universitet, Fundación Tatiana Pérez de Guzmán el Bueno, 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
Openalex Percentile: Top 56%
Down syndrome and intellectual disability research
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