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