The DROP-AD project: AD biomarkers from dry blood spots

BACKGROUND: In less than a decade, blood-based biomarkers for Alzheimer's disease (AD) have evolved from a promising research tool to a valuable clinical asset. Increased accessibility to biomarkers such as pTau217 could significantly enhance population screening, epidemiological studies, and the inclusion of underrepresented groups in dementia research. The DROP-AD project aims to streamline blood sample collection by introducing an alternative method that overcomes challenges associated with traditional venous draws while preserving biomarker integrity and value. METHOD: We recruited 344 participants (70.8 [11.7] years; 167 females [53.4%]) from eight centers, obtaining paired venous EDTA plasma and dried plasma spots (DPS) from capillary finger-stick collection. Capillary samples were shipped to Gothenburg, Sweden, without temperature control, extracted using a custom protocol, and analyzed with the ALZpath pTau217 Simoa assay. Cerebrospinal fluid (CSF) biomarkers were available for 151 individuals. Participants were classified as Aβ-positive (Aβ+) based on CSF Aβ42/pTau181 ratio. Cognitive assessments (MMSE and/or CDR-Global) were conducted for all participants. Statistical analyses included Spearman correlations, linear models, receiver operating characteristic (ROC) curve analysis, and evaluation of diagnostic performance using predefined cut-offs. RESULT: Capillary DPS pTau217 showed a strong correlation with venous plasma pTau217 across all cohorts (rs=0.74, 95% CI: 0.68-0.79; p <0.001). It was significantly associated with MMSE scores (r=-0.37; p <0.0001) and age (r=0.33, 95% CI; p <0.0001), mirroring the venous plasma results. Capillary DPS pTau217 was markedly elevated (+198%) in individuals with AD pathology, with a discriminative accuracy of 0.863 (95% CI: 0.81-0.92). For NfL (r=0.83, 95% CI: 0.74-0.89) and GFAP (r=0.773, 95% CI: 0.71-0.82), we observed strong correlations between capillary DPS and venous plasma measurements. In a subgroup of 31 participants with Down syndrome, capillary and venous blood biomarker levels were significantly correlated (GFAP: r=0.629, 95% CI: 0.35-0.81; pTau217: r=0.875, 95% CI: 0.50-0.97). Further ancillary studies will assess the reproducibility of DROP-AD across independent cohorts and evaluate its performance in self-guided collection settings. CONCLUSION: This study demonstrates the feasibility of detecting and accurately quantifying AD biomarkers from capillary blood. The results suggest that this simple and temperature-independent approach could facilitate the identification of individuals at high risk for AD pathology, broadening access to biomarker testing in research settings.