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@ARTICLE{Huber:285353,
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},
title = {{A} minimally invasive dried blood spot biomarker test for
the detection of {A}lzheimer's disease pathology.},
journal = {Nature medicine},
volume = {32},
number = {2},
issn = {1078-8956},
address = {[New York, NY]},
publisher = {Springer Nature},
reportid = {DZNE-2026-00219},
pages = {599 - 608},
year = {2026},
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 (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.},
keywords = {Humans / Alzheimer Disease: blood / Alzheimer Disease:
diagnosis / Alzheimer Disease: pathology / Dried Blood Spot
Testing: methods / Biomarkers: blood / Biomarkers:
cerebrospinal fluid / Female / tau Proteins: blood / Male /
Aged / Neurofilament Proteins: blood / Glial Fibrillary
Acidic Protein: blood / Aged, 80 and over / Middle Aged /
Phosphorylation / Biomarkers (NLM Chemicals) / tau Proteins
(NLM Chemicals) / Neurofilament Proteins (NLM Chemicals) /
neurofilament protein L (NLM Chemicals) / Glial Fibrillary
Acidic Protein (NLM Chemicals) / MAPT protein, human (NLM
Chemicals)},
cin = {AG Schneider},
ddc = {610},
cid = {I:(DE-2719)1011305},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41491101},
pmc = {pmc:PMC12920126},
doi = {10.1038/s41591-025-04080-0},
url = {https://pub.dzne.de/record/285353},
}