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

Abstract

Background: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPS^{v 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 DPS^venous 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 DPS^venous and plasma analytes correlated significantly, except for Aβ42. In the validation cohort, DPS^venous 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 DPS^venous 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 (DPS^venous). DPS^venous biomarkers correlated with standard procedures and cognitive status. DPS^venous biomarkers had a good diagnostic accuracy discriminating amyloid status. Our findings show the potential interchangeability of DPS^venous and plasma sampling. DPS^venous 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.