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@ARTICLE{Liu:280966,
author = {Liu, Ella and Jones, Sherri Lee and Light, Victoria and
Teunissen, Charlotte and Bouzigues, Arabella and Russell,
Lucy L and Foster, Phoebe H and Ferry-Bolder, Eve and van
Swieten, John C and Jiskoot, Lize C and Seelaar, Harro and
Sanchez-Valle, Raquel and Laforce, Robert and Graff,
Caroline and Galimberti, Daniela and Vandenberghe, Rik and
de Mendonça, Alexandre and Tiraboschi, Pietro and Santana,
Isabel and Gerhard, Alexander and Levin, Johannes and Sorbi,
Sandro and Otto, Markus and Butler, Chris R and Ber,
Isabelle Le and Finger, Elizabeth and Tartaglia, Maria
Carmela and Masellis, Mario and Rowe, James B and Synofzik,
Matthis and Moreno, Fermin and Borroni, Barbara and
Zetterberg, Henrik and Rohrer, Jonathan D and Ducharme,
Simon},
collaboration = {Signature, Banque},
othercontributors = {Initiative, Genetic Frontotemporal Dementia},
title = {{A}ccuracy of blood-based neurofilament light to different
genetic frontotemporal dementia from primary psychiatric
disorders.},
journal = {Journal of Alzheimer's disease},
volume = {106},
number = {4},
issn = {1387-2877},
address = {Amsterdam},
publisher = {IOS Press},
reportid = {DZNE-2025-01048},
pages = {1337 - 1354},
year = {2025},
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.},
keywords = {Humans / Frontotemporal Dementia: genetics / Frontotemporal
Dementia: blood / Frontotemporal Dementia: diagnosis / Male
/ Female / Middle Aged / Neurofilament Proteins: blood /
Aged / Adult / C9orf72 Protein: genetics / Diagnosis,
Differential / Aged, 80 and over / Biomarkers: blood /
Mental Disorders: blood / Mental Disorders: diagnosis /
Mental Disorders: genetics / Progranulins: genetics / tau
Proteins: genetics / Mutation: genetics / Sensitivity and
Specificity / Alzheimer's disease (Other) / biomarkers
(Other) / diagnosis (Other) / frontotemporal dementia
(Other) / neurofilament proteins (Other) / Neurofilament
Proteins (NLM Chemicals) / neurofilament protein L (NLM
Chemicals) / C9orf72 Protein (NLM Chemicals) / C9orf72
protein, human (NLM Chemicals) / Biomarkers (NLM Chemicals)
/ Progranulins (NLM Chemicals) / tau Proteins (NLM
Chemicals) / GRN protein, human (NLM Chemicals) / MAPT
protein, human (NLM Chemicals)},
cin = {AG Levin / Clinical Research (Munich)},
ddc = {610},
cid = {I:(DE-2719)1111016 / I:(DE-2719)1111015},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40605462},
pmc = {pmc:PMC12322341},
doi = {10.1177/13872877251352103},
url = {https://pub.dzne.de/record/280966},
}