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.