TY  - JOUR
AU  - Huber, Hanna
AU  - Montoliu-Gaya, Laia
AU  - Brum, Wagner S
AU  - Vávra, Jakub
AU  - Yakoub, Yara
AU  - Weninger, Haley
AU  - Braun-Wohlfahrt, Luisa Sophie
AU  - Simrén, Joel
AU  - Boada, Mercé
AU  - Ruiz, Agustín
AU  - Cano, Amanda
AU  - Orellana, Adelina
AU  - Valero, Sergi
AU  - Cañada, Laia
AU  - Tantinya, Natalia
AU  - Nogales, Ana Belen
AU  - Sanz-Cartagena, Pilar
AU  - Dittrich, Anna
AU  - Skoog, Ingmar
AU  - Sander-Long, Millie
AU  - Ballard, Clive
AU  - Richards, Megan
AU  - O'Leary, Mary
AU  - Clemmensen, Frederikke Kragh
AU  - Wandall, Hannah H D
AU  - Altomare, Daniele
AU  - Cantoni, Valentina
AU  - Stomrud, Erik
AU  - Palmqvist, Sebastian
AU  - Lleo, Alberto
AU  - Alcolea, Daniel
AU  - Carmona Iragui, Maria
AU  - Hernandez, Aida Sanjuan
AU  - Benejam, Bessy
AU  - Videla Toro, Laura
AU  - Singh, Alpana
AU  - Denkinger, Marisa N
AU  - Simonsen, Anja Hviid
AU  - Kern, Silke
AU  - Corbett, Anne
AU  - Fortea, Juan
AU  - Honigberg, Lee
AU  - Borroni, Barbara
AU  - Hansson, Oskar
AU  - Morató, Xavier
AU  - Blennow, Kaj
AU  - Zetterberg, Henrik
AU  - Ashton, Nicholas J
TI  - A minimally invasive dried blood spot biomarker test for the detection of Alzheimer's disease pathology.
JO  - Nature medicine
VL  - 32
IS  - 2
SN  - 1078-8956
CY  - [New York, NY]
PB  - Springer Nature
M1  - DZNE-2026-00219
SP  - 599 - 608
PY  - 2026
AB  - 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.
KW  - Humans
KW  - Alzheimer Disease: blood
KW  - Alzheimer Disease: diagnosis
KW  - Alzheimer Disease: pathology
KW  - Dried Blood Spot Testing: methods
KW  - Biomarkers: blood
KW  - Biomarkers: cerebrospinal fluid
KW  - Female
KW  - tau Proteins: blood
KW  - Male
KW  - Aged
KW  - Neurofilament Proteins: blood
KW  - Glial Fibrillary Acidic Protein: blood
KW  - Aged, 80 and over
KW  - Middle Aged
KW  - Phosphorylation
KW  - Biomarkers (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - Glial Fibrillary Acidic Protein (NLM Chemicals)
KW  - MAPT protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41491101
C2  - pmc:PMC12920126
DO  - DOI:10.1038/s41591-025-04080-0
UR  - https://pub.dzne.de/record/285353
ER  -