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Journal of the neurological sciences
Published

Plasma neurofilament light outperforms glial fibrillary acidic protein in differentiating behavioural variant frontotemporal dementia from primary psychiatric disorders

Authors

Dhamidhu Eratne, Matthew J Y Kang, Courtney Lewis, Christa Dang, Charles Malpas, Suyi Ooi, Amy Brodtmann, David Darby, Henrik Zetterberg, Kaj Blennow, Michael Berk, Olivia Dean, Chad Bousman, Naveen Thomas, Ian Everall, Chris Pantelis, Cassandra Wannan, Claudia Cicognola, Oskar Hansson, Shorena Janelidze, Alexander F Santillo, Dennis Velakoulis, MiND Study Group

Abstract

J Neurol Sci. 2024 Nov 8;467:123291. doi: 10.1016/j.jns.2024.123291. Online ahead of print.

ABSTRACT

OBJECTIVE: Timely, 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.

METHODS: We 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.

RESULTS: Plasma GFAP levels were significantly (all p < 0.001) elevated in bvFTD (n = 22, mean (M) = 273 pg/mL) compared to BPAD (n = 121, M = 96 pg/mL), MDD (n = 42, M = 105 pg/mL), TRS (n = 82, M = 67.9 pg/mL), and HC (n = 120, M = 76.8 pg/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 105 pg/mL was associated with 73 % specificity and 86 % sensitivity. NfL had AUC 0.95 [0.91, 0.99], 13.3 pg/mL cut-off, 88 % specificity, 86 % sensitivity, and was superior to GFAP (p = 0.02863) and combination of GFAP and NfL (p = 0.04726).

CONCLUSIONS: This 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.

PMID:39577322 | DOI:10.1016/j.jns.2024.123291

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg