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

Huber, Hanna ; Montoliu-Gaya, Laia ; Brum, Wagner S. ; Vávra, Jakub ; Yakoub, Yara ; Weninger, Haley ; Braun-Wohlfahrt, Luisa Sophie ; Simrén, Joel ; Boada, Mercé and Ruiz, Agustín , et al. (2026) In Nature Medicine 32(2). p.599-608
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... (More)

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 (rS = 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
32
issue
2
pages
10 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:105026688498
  • pmid:41491101
ISSN
1078-8956
DOI
10.1038/s41591-025-04080-0
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2026.
id
4495cc73-5aa7-4fbf-8484-609c90a4dac1
date added to LUP
2026-03-19 15:42:56
date last changed
2026-05-30 00:11:48
@article{4495cc73-5aa7-4fbf-8484-609c90a4dac1,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Huber, Hanna and Montoliu-Gaya, Laia and Brum, Wagner S. and Vávra, Jakub and Yakoub, Yara and Weninger, Haley and Braun-Wohlfahrt, Luisa Sophie and Simrén, Joel and Boada, Mercé and Ruiz, Agustín and Cano, Amanda and Orellana, Adelina and Valero, Sergi and Cañada, Laia and Tantinya, Natalia and Nogales, Ana Belen and Sanz-Cartagena, Pilar and Dittrich, Anna and Skoog, Ingmar and Sander-Long, Millie and Ballard, Clive and Richards, Megan and O’Leary, Mary and Clemmensen, Frederikke Kragh and Wandall, Hannah H.D. and Altomare, Daniele and Cantoni, Valentina and Stomrud, Erik and Palmqvist, Sebastian and Lleo, Alberto and Alcolea, Daniel and Carmona Iragui, Maria and Hernandez, Aida Sanjuan and Benejam, Bessy and Videla Toro, Laura and Singh, Alpana and Denkinger, Marisa N. and Simonsen, Anja Hviid and Kern, Silke and Corbett, Anne and Fortea, Juan and Honigberg, Lee and Borroni, Barbara and Hansson, Oskar and Morató, Xavier and Blennow, Kaj and Zetterberg, Henrik and Ashton, Nicholas J.}},
  issn         = {{1078-8956}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{599--608}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{A minimally invasive dried blood spot biomarker test for the detection of Alzheimer’s disease pathology}},
  url          = {{http://dx.doi.org/10.1038/s41591-025-04080-0}},
  doi          = {{10.1038/s41591-025-04080-0}},
  volume       = {{32}},
  year         = {{2026}},
}