Journal Article

DZNE-2025-01048

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Accuracy of blood-based neurofilament light to different genetic frontotemporal dementia from primary psychiatric disorders.

Liu, E. ; Jones, S. L. ; Light, V. ; Teunissen, C. ; Bouzigues, A. ; Russell, L. L. ; Foster, P. H. ; Ferry-Bolder, E. ; van Swieten, J. C. ; Jiskoot, L. C. ; Seelaar, H. ; Sanchez-Valle, R. ; Laforce, R. ; Graff, C. ; Galimberti, D. ; Vandenberghe, R. ; de Mendonça, A. ; Tiraboschi, P. ; Santana, I. ; Gerhard, A. ; Levin, J.DZNE* ; Sorbi, S. ; Otto, M. ; Butler, C. R. ; Ber, I. L. ; Finger, E. ; Tartaglia, M. C. ; Masellis, M. ; Rowe, J. B. ; Synofzik, M.Extern* ; Moreno, F. ; Borroni, B. ; Zetterberg, H. ; Rohrer, J. D. ; Ducharme, S. ; Initiative, G. F. D. (GENFI) ; Signature, B. (Collaboration Author)

2025
IOS Press Amsterdam

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Please use a persistent id in citations: doi:10.1177/13872877251352103

Abstract: BackgroundGenetic frontotemporal dementia (FTD) along with Alzheimer's disease (AD), is one of the most prevalent early-onset dementias. The differential diagnosis of FTD from primary psychiatric disorder (PPD) has been challenging due to significant symptom overlap, particular as FTD often presents with prolonged psychiatric prodromes.ObjectiveThis study aims to evaluate whether blood-based neurofilament light chain (NfL) can differentiate genetic FTD from PPD, and to determine a global clinical cutoff to differentiate genetic FTD carriers from PPD with high specificity and sensitivity.MethodsData (ages 40-81) were obtained from FTD mutation carriers (GENFI; n = 474; n = 120 C9orf72, n = 114 GRN, n = 50 MAPT, n = 190 controls), and PPD (Biobanque Signature; n = 848). Blood-based NfL was measured with SIMOA HD-X (BbS) and SIMOA HD-1 (GENFI).ResultsBlood-based NfL was higher in all symptomatic mutations compared to PPD. Mildly symptomatic (0 < FTLD CDR-SOB-NM < 4) C9orf72 and GRN carriers also had higher NfL. ROC curve revealed an optimal blood-based NfL cutoff of 22.1 pg/mL (J = 0.647) to distinguish symptomatic genetic FTD from PPD (78.5% sensitivity, 86.2% specificity, AUC = 0.908). For mildly symptomatic subjects, a cutoff of 16.2 pg/mL (J = 0.601) differentiated groups with 86.7% sensitivity and 73.5% specificity (AUC = 0.870).ConclusionsNfL holds potential as a blood-based biomarker for symptomatic genetic FTD carriers, with moderate accuracy to distinguish PPD from mild forms including C9orf72.

Keyword(s): Humans (MeSH) ; Frontotemporal Dementia: genetics (MeSH) ; Frontotemporal Dementia: blood (MeSH) ; Frontotemporal Dementia: diagnosis (MeSH) ; Male (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Neurofilament Proteins: blood (MeSH) ; Aged (MeSH) ; Adult (MeSH) ; C9orf72 Protein: genetics (MeSH) ; Diagnosis, Differential (MeSH) ; Aged, 80 and over (MeSH) ; Biomarkers: blood (MeSH) ; Mental Disorders: blood (MeSH) ; Mental Disorders: diagnosis (MeSH) ; Mental Disorders: genetics (MeSH) ; Progranulins: genetics (MeSH) ; tau Proteins: genetics (MeSH) ; Mutation: genetics (MeSH) ; Sensitivity and Specificity (MeSH) ; Alzheimer's disease ; biomarkers ; diagnosis ; frontotemporal dementia ; neurofilament proteins ; Neurofilament Proteins ; neurofilament protein L ; C9orf72 Protein ; C9orf72 protein, human ; Biomarkers ; Progranulins ; tau Proteins ; GRN protein, human ; MAPT protein, human

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Contributing Institute(s):

1. Clinical Neurodegeneration (AG Levin)
2. Clinical Research (Munich) (Clinical Research (Munich))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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