A minimally invasive dried blood spot biomarker test for the detection of Alzheimer's disease pathology
Por:
Huber, H, Montoliu-Gaya, L, Brum, WS, Vávra, J, Yakoub, Y, Weninger, H, Braun-Wohlfahrt, LS, Simrén, J, Boada, M, Ruiz, A, Cano, A, Orellana, A, Valero, S, Cañada, L, Tantinya, N, Nogales, AB, Sanz-Cartagena, P, Dittrich, A, Skoog, I, Sander-Long, M, Ballard, C, Richards, M, O'Leary, M, Clemmensen, FK, Wandall, HHD, Altomare, D, Cantoni, V, Stomrud, E, Palmqvist, S, Lleo, A, Alcolea, D, Iragui, MC, Hernandez, AS, Benejam, B, Toro, LV, Singh, A, Denkinger, MN, Simonsen, AH, Kern, S, Corbett, A, Fortea, J, Honigberg, L, Borroni, B, Hansson, O, Morató, X, Blennow, K, Zetterberg, H, Ashton, NJ
Publicada:
1 feb 2026
Ahead of Print:
1 ene 2026
Resumen:
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.
Filiaciones:
Huber, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
German Ctr Neurodegenerat Dis, Bonn, Germany
Univ Hosp Bonn, Dept Old Age Psychiat & Cognit Disorders, Bonn, Germany
Montoliu-Gaya, L:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Brum, WS:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Univ Fed Rio Grande do Sul, Grad Program Biol Sci Biochem, Porto Alegre, RS, Brazil
Vávra, J:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Yakoub, Y:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
McGill Univ, Integrated Program Neurosci, Montreal, PQ, Canada
Douglas Mental Hlth Univ Inst, Res Ctr, Montreal, PQ, Canada
Weninger, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Braun-Wohlfahrt, LS:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Simrén, J:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Boada, M:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Ruiz, A:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Cano, A:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Orellana, A:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Valero, S:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Cañada, L:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Tantinya, N:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Nogales, AB:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Sanz-Cartagena, P:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Dittrich, A:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Neuropsychiat, Molndal, Sweden
Skoog, I:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Neuropsychiat, Molndal, Sweden
Sander-Long, M:
Univ Exeter, Coll Med & Hlth, Exeter, Devon, England
Ballard, C:
Univ Exeter, Coll Med & Hlth, Exeter, Devon, England
Richards, M:
Univ Exeter, Coll Med & Hlth, Exeter, Devon, England
O'Leary, M:
Univ Exeter, Coll Med & Hlth, Exeter, Devon, England
Clemmensen, FK:
Copenhagen Univ Hosp, Rigshospitalet, Danish Dementia Res Ctr, Dept Neurol, Copenhagen, Denmark
Wandall, HHD:
Copenhagen Univ Hosp, Rigshospitalet, Danish Dementia Res Ctr, Dept Neurol, Copenhagen, Denmark
Altomare, D:
Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy
Univ Appl Sci & Arts Southern Switzerland SUPSI, CCA, Dept Business Econ Hlth & Social Care DEASS, Manno, Switzerland
Cantoni, V:
Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy
Stomrud, E:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Skane Univ Hosp, Memory Clin, Malmo, Sweden
Palmqvist, S:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Skane Univ Hosp, Memory Clin, Malmo, Sweden
Lleo, A:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Alcolea, D:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Iragui, MC:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Down Med Ctr, Barcelona, Spain
Hernandez, AS:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Down Med Ctr, Barcelona, Spain
Benejam, B:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Down Med Ctr, Barcelona, Spain
Toro, LV:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Down Med Ctr, Barcelona, Spain
Singh, A:
Banner Sun Hlth Res Inst, Sun City, AZ 85351 USA
Denkinger, MN:
Banner Sun Hlth Res Inst, Sun City, AZ 85351 USA
Simonsen, AH:
Copenhagen Univ Hosp, Rigshospitalet, Danish Dementia Res Ctr, Dept Neurol, Copenhagen, Denmark
Kern, S:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Reg Vastra Gotaland, Dept Neuropsychiat, Molndal, Sweden
Univ Gothenburg, Ctr Ageing & Hlth AGECAP, Neuropsychiat Epidemiol Unit,Sahlgrenska Acad, Dept Psychiat & Neurochem,Inst Neurosci & Physiol, Molndal, Sweden
Corbett, A:
Univ Exeter, Coll Med & Hlth, Exeter, Devon, England
Fortea, J:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau, Dept Neurol, St Pau Memory Unit, Barcelona, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, CIBERNED, Barcelona, Spain
Fundacio Catalana Sindrome, Barcelona Down Med Ctr, Barcelona, Spain
Honigberg, L:
AlZpath Inc, Carlsbad, CA USA
Borroni, B:
Univ Brescia, Dept Clin & Expt Sci, Brescia, Italy
IRCCS Ist Ctr San Giovanni Dio Fatebenefratelli, Mol Markers Lab, Brescia, Italy
Hansson, O:
Lund Univ, Dept Clin Sci Malmo, Clin Memory Res Unit, Lund, Sweden
Morató, X:
Univ Int Catalunya, Ace Alzheimer Ctr Barcelona, Barcelona, Spain
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid, Spain
Blennow, K:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
Sorbonne Univ, Pitie Salpetriere Hosp, Paris Brain Inst, ICM, Paris, France
Univ Sci & Technol China, Div Life Sci & Med, Inst Aging & Brain Disorders, Neurodegenerat Disorder Res Ctr, Hefei, Peoples R China
Univ Sci & Technol China, Inst Aging & Brain Disorders, Dept Neurol, Hefei, Peoples R China
USTC, Affiliated Hosp 1, Hefei, Peoples R China
UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England
Zetterberg, H:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Sahlgrens Univ Hosp, Clin Neurochem Lab, Molndal, Sweden
UCL, UK Dementia Res Inst, London, England
Hong Kong Ctr Neurodegenerat Dis, InnoHK, Hong Kong, Peoples R China
Univ Wisconsin Madison, Wisconsin Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI USA
Indian Inst Sci, Ctr Brain Res, Bangalore, India
Ashton, NJ:
Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Psychiat & Neurochem, Molndal, Sweden
Banner Sun Hlth Res Inst, Sun City, AZ 85351 USA
Banner Alzheimers Inst, Phoenix, AZ 85006 USA
Univ Arizona, Phoenix, AZ 85721 USA
Green Submitted, hybrid
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