Plasma glial fibrillary acidic protein and neurofilament light chain in behavioural variant frontotemporal dementia and primary psychiatric disorders

ObjectiveTimely, accurate distinction between behavioural variant frontotemporal dementia (bvFTD) and primary psychiatric disorders (PPD) is a clinical challenge. Blood biomarkers such as neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have shown promise. Prior work has shown NfL helps distinguish FTD from PPD. Few studies have assessed NfL together with GFAP. MethodsWe investigated plasma GFAP and NfL levels in participants with bvFTD, bipolar affective disorder (BPAD), major depressive disorder (MDD), treatment-resistant schizophrenia (TRS), healthy controls (HC), adjusting for age and sex. We compared ability of GFAP and NfL to distinguish bvFTD from PPD. ResultsPlasma GFAP levels were significantly (all p<0.001) elevated in bvFTD (n=22, mean (M)=273pg/mL) compared to BPAD (n=121, M=96pg/mL), MDD (n=42, M=105pg/mL), TRS (n=82, M=67.9pg/mL), and HC (n=120, M=76.8pg/mL). GFAP distinguished bvFTD from all PPD with an area under the curve (AUC) of 0.85, 95% confidence interval [0.76, 0.95]. The optimal cut-off of 105pg/mL was associated with 73% specificity and 86% sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3pg/mL cut-off, 88% specificity, 86% sensitivity, and was superior to GFAP (p=0.02863) and combination of GFAP and NfL (p=0.04726). ConclusionsThis study found elevated GFAP levels in bvFTD compared to a large cohort of PPD, but NfL levels exhibited better performance in this distinction. These findings extend the literature on GFAP in bvFTD and build evidence for plasma NfL as a useful biomarker to assist with distinguishing bvFTD from PPD. Utilisation of NfL may improve timely and accurate diagnosis of bvFTD.