BACKGROUND:
Frontotemporal dementia (FTD) is a heterogeneous group of disorders involving frontal and temporal lobe degeneration, with overlapping clinical, genetic, and pathological features. Blood-based biomarkers, including Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP), hold promise for improving differential diagnoses. NfL is consistently elevated in symptomatic carriers, rising sharply just prior to phenoconversion, whilst GFAP is commonly increased in certain subgroups such as those with GRN mutations. Biomarker validation across platforms is essential for diagnostic accuracy, disease monitoring, and evaluating emerging therapies. Despite comparisons between NULISA and established assays, no studies have focused solely on FTD.
METHODS:
Comparative analysis of blood NfL and GFAP in a genetic FTD cohort was performed (GENFI, n=448). Samples collected simultaneously were analysed on the nucleic acid linked immuno‐sandwich assay (NULISA) and the single molecule array (Simoa). Comparisons were grouped by genetic mutation (C9ORF72, MAPT, and GRN), genetic status (non-carrier vs carrier) and symptom status (control, pre-symptomatic, and fully symptomatic on the CDR + NACC FTLD rating scale).
RESULTS:
NfL and GFAP showed strong agreement (ρ = 0.84-0.98), with correlations increasing with clinical severity (NfL ρ = 0.87 (controls), 0.93 (presymptomatic), 0.96 (symptomatic); GFAP ρ = 0.82, 0.90, 0.93). Both biomarkers showed highest correlation in GRN mutations (ρ = 0.98 for both) and stronger correlations in mutation carriers vs non-carriers (NfL ρ = 0.96 vs 0.91; GFAP ρ = 0.92 vs 0.84). ROC analyses showed comparable discrimination between mutation carriers and non-carriers (AUC = 0.61-0.68) and excellent accuracy for distinguishing non-carriers from symptomatic individuals (AUC = 0.82-0.93).
CONCLUSION:
NfL and GFAP exhibited strong platform correlations, increasing alongside clinical severity and supporting stage-specific diagnosis. ROC analysis confirmed excellent accuracy in identifying symptomatic individuals. Findings support NfL and GFAP as robust biomarkers for FTD diagnosis and monitoring, with clinical and research applications.