ABSTRACT
Introduction:
The exclusion of affected
populations from
Alzheimer's disease (AD) clinical
research limits our
understanding of
disease heterogeneity and its impact on clinical care. While micro sampling with dried
plasma spots (DPS) can promote inclusivity by enabling sample collection in
remote areas, current
techniques lack the
sensitivity required for the quantification of phosphorylated tau at Thr181 (pTau-181) in DPS extracts.
Methods:
We developed an assay for pTau-181 with reduced bead count and improved bead read
efficiency (BRE) using a prototype Simoa instrument. This novel assay's performance was evaluated against standard pTau-181 assays on two Simoa platforms, and DPS extracts were tested for pTau-181 quantification feasibility.
Results:
The novel assay quantifies pTau-181 at concentrations up to 16x lower than traditional pTau-181 assays on HD-X and SR-X platforms. DPS extracts tested with our low-bead assay were quantified considerably above the lower limit of quantification (LLOQ), indicating the suitability of this assay for
future DPS extract measurements.
Discussion:
Implementing DPS sampling and pTau-181 quantification could increase participation from underrepresented groups in AD
research. However, additional assay
optimization and an in-depth study of preanalytical sample stability are essential for the transition to clinical applicability.