Biomarkers

Background: Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer disease (AD) pathology, with p-tau217 having the greatest utility. Increased and simplified access to blood biomarkers is crucial for early diagnosis, proper patient management and prompt initiation of disease-modifying treatments. The DROP-AD project investigates the capability of finger-prick collection to accurately measure p-tau217, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP).

Method: In this prospective study, n=230 participants (mean[SD] age, 71.0 [10] years; 138 females [60.0%]) were recruited from four participating centers. Capillary whole blood was obtained by finger-prick into three devices (Noviplex^®; Capitainer^® Plasma; Capitainer^® B50); not all patients completed all capillary sampling. Capillary cards were shipped to Gothenburg, without temperature control. Samples were extracted by a custom protocol and measured by Simoa. EDTA plasma was collected in all participants; cerebrospinal fluid (CSF) biomarkers were available in 141 individuals. Participants were defined as Aβ positive (Aβ+) using two strategies: a plasma p-tau217 (ALZpath) >0.63 pg/mL indicating high-risk^[1] and CSF Aβ42/40 <0.063. Statistical analysis included linear regressions, Mann-Whitney U tests and receiver operating characteristic (ROC) area under the curve (AUC) analyses.

Result: A significant correlation was found for finger-prick and EDTA plasma for all tested biomarkers (GFAP[n=98], R²=0.714; NfL[n=75], R²=0.625; p-tau217[n=73], R²=0.561; all P<0.0001). When Aβ+ was defined by plasma p-tau217, finger-prick p-tau217 was increased in Aβ+ (mean[SD], 0.033 pg/mL [0.02]) compared to Aβ- patients (0.016 pg/mL [0.03], fold-change mean[SD], 1.9 [1.5], [n=73], U=175.5, P<0.0001) with high diagnostic accuracy (AUC[95% CI] = 0.867 [0.785-0.949]). Finger-prick GFAP was also significantly increased in Aβ+ ([n=35], U=38, P=0.002, AUC=0.838 [0.687-0.988]). In identifying CSF Aβ+, lower accuracies were observed (p-tau217[n=58], AUC=0.831 [0.712-0.949]; GFAP[n=33], AUC=0.714 [0.524-0.904]) but not statistically different from EDTA plasma. Finger-prick p-tau217 and GFAP also associated with cognitive performance (CDR_global; p-tau217[n=62], R²=0.1011, P=0.0118; GFAP[n=94], R²=0.1679, P<0.0001).

Conclusion: This study demonstrates the potential of measuring AD blood biomarkers, including p-tau217, NfL and GFAP, from finger-prick collection. We speculate that this simple, self-executable, temperature-independent, and reliable method could identify individuals of high risk of AD pathology (p-tau217) and has potential application for multiple neurodegenerative diseases (NfL and GFAP). ^[1]Ashton 2024, JAMA Neurol.