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. 2024 Apr;20(4):2340-2352.
doi: 10.1002/alz.13697. Epub 2024 Jan 29.

Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings

Hanna Huber  1 , Kaj Blennow  1   2 , Henrik Zetterberg  1   2   3   4   5   6 , Mercé Boada  7   8 , Andreas Jeromin  9 , Haley Weninger  1 , Raul Nuñez-Llaves  8 , Núria Aguilera  8 , Maribel Ramis  8 , Joel Simrén  1 , Johanna Nilsson  1 , Juan Lantero-Rodriguez  1 , Adelina Orellana  8 , Fernando García-Gutiérrez  8 , Xavier Morató  7   8 , Nicholas J Ashton  1   10   11 , Laia Montoliu-Gaya  1
Affiliations

Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings

Hanna Huber et al. Alzheimers Dement. 2024 Apr.

Abstract

Background: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPSv enous) for the diagnosis and monitoring of neurodegenerative diseases in remote settings.

Methods: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p-tau181 and p-tau217) were measured in paired DPSvenous and ethylenediaminetetraacetic acid plasma samples with single-molecule array. In the validation cohort, a subset of participants (n = 99) had cerebrospinal fluid (CSF) biomarkers.

Results: All DPSvenous and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPSvenous GFAP, NfL, p-tau181, and p-tau217 differed between CSF Aβ-positive and -negative individuals and were associated with worsening cognition.

Discussion: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPSvenous extends the utility of blood-based biomarkers to remote settings with simplified sampling conditions, storage, and logistics.

Highlights: A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPSvenous). DPSvenous biomarkers correlated with standard procedures and cognitive status. DPSvenous biomarkers had a good diagnostic accuracy discriminating amyloid status. Our findings show the potential interchangeability of DPSvenous and plasma sampling. DPSvenous may facilitate remote and temperature-independent sampling for AD biomarker measurement. Innovative tools for blood biomarker sampling may help recognizing the earliest changes of AD.

Keywords: Alzheimer's disease; amyloid beta; biomarkers; blood; dried blood spots; dried plasma spots; glial fibrillary acidic protein; neurodegeneration; neurofilament light; phosphorylated tau; plasma; remote sampling; temperature‐independent sampling.

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Conflict of interest statement

N.J.A. has given lectures in symposia sponsored by Eli‐lily, Roche Diagnostics, and Quanterix. K.B. has served as a consultant, on advisory boards, or on data monitoring committees for Abcam, Axon, BioArctic, Biogen, JOMDD/Shimadzu, Julius Clinical, Lilly, MagQu, Novartis, Ono Pharma, Pharmatrophix, Prothena, Roche Diagnostics, and Siemens Healthineers, and is a cofounder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. H.Z. has served on scientific advisory boards and/or as a consultant for Abbvie, Acumen, Alector, Alzinova, Amylyx, ALZpath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche; and is a co‐founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program outside the submitted work. A.J. is an employee of ALZpath, Inc., and has stock options. M.B. is an employee of ACE Alzheimer Center and is a member of the Advisory Boards Grifols, Roche, Lilly, Araclon Biotech, Merck, Zambon, Biogen, Novo‐Nordisk, Bioiberica, Eisai, Servier, and Schwabe Pharma. R.N.L., N.A., M.R., A.O., F.G.G., and X.M. are employees of ACE Alzheimer Center with no conflicts of interest. The remaining authors have no conflicts of interests to declare. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Correlation between EDTA plasma levels and GFAP (A), NfL (B), Aβ40 (C), Aβ42 (D), Aβ42/40 (E), p‐tau181 (F), and p‐tau217 (G) levels from DPSvenous in the discovery cohort. Aβ, amyloid‐beta; DPS, dried plasma spots; EDTA, ethylenediaminetetraacetic acid; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; p‐tau, phosphorylated tau.
FIGURE 2
FIGURE 2
Correlation between EDTA plasma levels and GFAP (A), NfL (B), Aβ40 (C), Aβ42 (D), Aβ42/40 (E), p‐tau181 (F), and p‐tau217 (G) levels from DPSvenous in the validation cohort. Aβ, amyloid beta; DPS, dried plasma spots; EDTA, ethylenediaminetetraacetic acid; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; p‐tau, phosphorylated tau.
FIGURE 3
FIGURE 3
GFAP (A), NfL (B), Aβ40 (C), Aβ42 (D), p‐tau181 (E), and p‐tau217 (F) levels from DPSvenous (left) and EDTA plasma (right) in amyloid‐positive (A+) and amyloid‐negative (A–) individuals in the validation cohort. Differences between the groups were tested using two‐sided t tests, results are indicated as follows: ****: P < 0.0001; ***: P < 0.001; **: P < 0.01; *: P < 0.05; ns: P ≥ 0.05. A+/A– status was evaluated using CSF Aβ42/40 cut‐offs. A+ indicates Aβ positivity; A– indicates Aβ negativity. Aβ, amyloid‐beta; CSF, cerebrospinal fluid; DPS, dried plasma spots; EDTA, ethylenediaminetetraacetic acid; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; p‐tau, phosphorylated tau.
FIGURE 4
FIGURE 4
DPSvenous GFAP (A), NfL (B), Aβ40 (C), Aβ42 (D), p‐tau181 (E), and p‐tau217 (F) in individuals with high (CDR ≤ 0.5) and low (CDR ≥ 1) cognitive performance in the validation cohort. Differences between the groups were tested using two‐sided t tests and are indicated as follows: ***: P < 0.001; **: P < 0.01; *: P < 0.05; ns: P ≥ 0.05. Aβ, amyloid‐beta; CDR, Clinical Dementia Rating scale; DPS, dried plasma spots; GFAP, glial fibrillary acidic protein; NfL, neurofilament light; p‐tau, phosphorylated tau.
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