Liu, Ella;
Jones, Sherri Lee;
Light, Victoria;
Teunissen, Charlotte;
Bouzigues, Arabella;
Russell, Lucy L;
Foster, Phoebe H;
... Ducharme, Simon; + view all
(2025)
Accuracy of blood-based neurofilament light to different genetic frontotemporal dementia from primary psychiatric disorders.
Journal of Alzheimer’s Disease
, 106
(4)
pp. 1337-1354.
10.1177/13872877251352103.
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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.
| Type: | Article |
|---|---|
| Title: | Accuracy of blood-based neurofilament light to different genetic frontotemporal dementia from primary psychiatric disorders |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1177/13872877251352103 |
| Publisher version: | https://doi.org/10.1177/13872877251352103 |
| Language: | English |
| Additional information: | © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/). |
| Keywords: | Alzheimer's disease, biomarkers, diagnosis, frontotemporal dementia, neurofilament proteins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212734 |
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