A minimally invasive dried blood spot biomarker test for the detection of Alzheimer’s disease pathology

Blood biomarkers have emerged as accurate tools for detecting Alzheimer's disease (AD) pathology, offering a minimally invasive alternative to traditional diagnostic methods such as imaging and cerebrospinal fluid (CSF) analysis. Yet, the logistics surrounding venipuncture for blood collection, although considerably simpler than the acquisition of imaging and CSF, require precise processing and storage specific to AD biomarkers that are still guided by medical personnel. Consequently, limitations in their widescale use in research and broader clinical implementation exist. The DROP-AD project investigates the potential of dried plasma spot (DPS) and dried blood spot (DBS) analysis, derived from capillary blood, for detecting AD biomarkers, including phosphorylated tau at amino acid 217 (p-tau217), glial fibrillary acidic protein and neurofilament light. Here, 337 participants from 7 centers were included, with 304 participants providing paired capillary DPS or DBS and venous plasma samples. We observed strong correlations between DPS p-tau217 and venous plasma p-tau217 (r<sub>S</sub> = 0.74, P < 0.001). DPS p-tau217 progressively increased with increasing disease severity, and showed good accuracy in predicting CSF biomarker positivity (area under the curve = 0.864). Similarly, we demonstrated the successful detection of glial fibrillary acidic protein and neurofilament light with strong correlations between DBS and DPS, respectively, using paired venous plasma samples. Notably, the method was also effective in individuals with Down syndrome, a population at high genetic risk for AD but in whom standard blood sampling by venipuncture may be more complicated, revealing elevated biomarkers in those with dementia compared with asymptomatic individuals. The study also explored unsupervised blood collection, finding high concordance between supervised and self-collected samples. These findings underscore the potential of dried blood collection and capillary blood as a minimally invasive, scalable approach for AD biomarker testing in research settings. Yet, further refinement of collection and analytical protocols is needed to fully translate this approach to be viable and useful as a clinical tool.

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Publication Details

Journal
Nature Medicine
Published
2026-01-05
DOI
https://doi.org/10.1038/s41591-025-04080-0
Citations
4
Primary Topic
Advanced Proteomics Techniques and Applications
Type
article
Field-Weighted Citation Impact
65.05

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article

A minimally invasive dried blood spot biomarker test for the detection of Alzheimer’s disease pathology

I. Skoog, Hanna Huber, Joel Simrén, Erik Stomrud et al.
4 citations
Nature Medicine
Advanced Proteomics Techniques and Applications
65.05
article

A minimally invasive dried blood spot biomarker test for the detection of Alzheimer’s disease pathology

I. Skoog, Hanna Huber, Joel Simrén, Erik Stomrud, Lee Honigberg, Frederikke Kragh Clemmensen, Adelina Orellana, Wagner S. Brum, Clive Ballard, A. B. Nogales, María Carmona Iragui, Yara Yakoub, Anna Dittrich, Daniele Altomare, Valentina Cantoni, Kaj Blennow, Natàlia Tantinyá, Haley Weninger, Barbara Borroni, Marisa N. Denkinger, Oskar H. Hansson, Juan M. Fortea, Xavier Cuadras Morató, Daniel Alcolea, Laia Cañada, Alberto Lleó, Laura Videla Toro, Pilar Sanz-Cartagena, Luisa Sophie Braun-Wohlfahrt, Millie Sander-Long, Anne Corbett, Alpana Singh, Sergi Valero, Megan Richards, Jakub Vávra, Anja Hviid Simonsen, Henrik Zetterberg, Bessy Benejam, Hannah H. D. Wandall, Laia Montoliu-Gaya, Aida Sanjuan Hernandez, Mercè Boada, Agustin Ruiz, Amanda Cano, Mary O’Leary, Silke Kern, Nicholas J. Ashton, Sebastian Palmqvist
article en
4 citations

Abstract

Blood biomarkers have emerged as accurate tools for detecting Alzheimer's disease (AD) pathology, offering a minimally invasive alternative to traditional diagnostic methods such as imaging and cerebrospinal fluid (CSF) analysis. Yet, the logistics surrounding venipuncture for blood collection, although considerably simpler than the acquisition of imaging and CSF, require precise processing and storage specific to AD biomarkers that are still guided by medical personnel. Consequently, limitations in their widescale use in research and broader clinical implementation exist. The DROP-AD project investigates the potential of dried plasma spot (DPS) and dried blood spot (DBS) analysis, derived from capillary blood, for detecting AD biomarkers, including phosphorylated tau at amino acid 217 (p-tau217), glial fibrillary acidic protein and neurofilament light. Here, 337 participants from 7 centers were included, with 304 participants providing paired capillary DPS or DBS and venous plasma samples. We observed strong correlations between DPS p-tau217 and venous plasma p-tau217 (r<sub>S</sub> = 0.74, P < 0.001). DPS p-tau217 progressively increased with increasing disease severity, and showed good accuracy in predicting CSF biomarker positivity (area under the curve = 0.864). Similarly, we demonstrated the successful detection of glial fibrillary acidic protein and neurofilament light with strong correlations between DBS and DPS, respectively, using paired venous plasma samples. Notably, the method was also effective in individuals with Down syndrome, a population at high genetic risk for AD but in whom standard blood sampling by venipuncture may be more complicated, revealing elevated biomarkers in those with dementia compared with asymptomatic individuals. The study also explored unsupervised blood collection, finding high concordance between supervised and self-collected samples. These findings underscore the potential of dried blood collection and capillary blood as a minimally invasive, scalable approach for AD biomarker testing in research settings. Yet, further refinement of collection and analytical protocols is needed to fully translate this approach to be viable and useful as a clinical tool.

Nature MedicineVol. 32(2)
University of Science and Technology of China (CN), Universidade Federal do Rio Grande do Sul (BR), University of Wisconsin–Madison (US), University of Applied Sciences and Arts of Southern Switzerland (CH), Lund University (SE), University of Exeter (GB), University Hospital Bonn (DE), Douglas Mental Health University Institute (CA), Sahlgrenska University Hospital (SE), Instituto de Salud Carlos III (ES), German Center for Neurodegenerative Diseases (DE), Hospital de Sant Pau (ES), Banner Health (US), Copenhagen University Hospital (DK), Rigshospitalet (DK), Universitat Internacional de Catalunya (ES), Sorbonne Université (FR), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Centro San Giovanni di Dio Fatebenefratelli (IT), Pitié-Salpêtrière Hospital (FR), UK Dementia Research Institute (GB), Skåne University Hospital (SE), Banner Sun Health Research Institute (US), Institut du Cerveau (FR), University College London (GB), McGill University (CA), Indian Institute of Science Bangalore (IN), University of Brescia (IT), University of Gothenburg (SE)
Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Gun och Bertil Stohnes Stiftelse, Demensförbundet, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, Global Brain Health Institute, European Partnership on Metrology, National Institute for Health and Care Research, Department of Health and Social Care, University College London, European Commission, Deutsche Forschungsgemeinschaft, Fondation Jérôme Lejeune, Lunds Universitet, Hjärnfonden, Vetenskapsrådet, Göteborgs Universitet, Stiftelsen Psykiatriska Forskningsfonden, Alzheimerfonden, Ministerio de Asuntos Económicos y Transformación Digital, Gobierno de España, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, UK Dementia Research Institute, Olav Thon Stiftelsen, Stiftelsen Bundy Academy, Fondation pour la Recherche sur Alzheimer, HORIZON EUROPE Framework Programme, Instituto de Salud Carlos III, European Regional Development Fund
Openalex Percentile: Top 0%
Advanced Proteomics Techniques and Applications
65.05
DOIOpen Access PDFOpenAlex
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