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@ARTICLE{Hermann:163435,
author = {Hermann, Peter and Canaslan, Sezgi and Villar-Piqué, Anna
and Bunck, Timothy and Goebel, Stefan and Llorens Torres,
Francesc Josep and Schmitz, Matthias and Zerr, Inga},
title = {{P}lasma neurofilament light chain as a biomarker for fatal
familial insomnia.},
journal = {European journal of neurology},
volume = {29},
number = {6},
issn = {1351-5101},
address = {Oxford},
publisher = {Blackwell Science},
reportid = {DZNE-2022-00195},
pages = {1841-1846},
year = {2022},
note = {ISSN 1468-1331 not unique: **2 hits**. (CC BY-NC)},
abstract = {Fatal familial insomnia is a rare hereditary prion disease
associated with the D178N-129M PRNP mutation. Early
diagnosis is difficult, because the clinical syndrome may
overlap with affective disorders. In addition, most known
cerebrospinal fluid biomarkers for prion diseases and
magnetic resonance imaging do not show a good diagnostic
accuracy for fatal familial insomnia. In this context, data
on plasma biomarkers are scarce.We analyzed levels of
neurofilament light chain, glial fibrillary acidic protein,
chitinase-3-like protein 1, calcium-binding protein B, and
total tau protein in six serial plasma samples from a
patient with fatal familial insomnia. Subsequently, plasma
neurofilament light chain was analyzed in n = 25 patients
and n = 19 controls. The diagnostic accuracy and
associations with disease stage and duration were
explored.Among all biomarker candidates in the case study,
only neurofilament light chain levels showed a constant
evolution and increased over time. They discriminated fatal
familial insomnia from controls with an area under the curve
of 0.992 $(95\%$ confidence interval [CI] = 0.974-1) in the
case-control study. Higher concentrations were associated
with methionine homozygosity at codon 129 PRNP (p = 0.006),
shorter total disease duration (rho = -0.467, p = 0.019,
$95\%$ CI = -0.790 to -0.015), and shorter time from
sampling to death (rho = -0.467, p = 0.019, $95\%$ CI =
-0.773 to -0.019).Plasma neurofilament light chain may be a
valuable minimally invasive diagnostic biomarker for fatal
familial insomnia after clinical onset. Most important,
stage-related increase and association with disease duration
indicate potential as a prognostic marker and as a surrogate
marker in clinical trials.},
keywords = {Biomarkers / Case-Control Studies / Humans / Insomnia,
Fatal Familial: diagnosis / Insomnia, Fatal Familial:
genetics / Intermediate Filaments / Prion Diseases: genetics
/ biomarker (Other) / fatal familial insomnia (Other) /
neurofilament light chain (Other) / plasma (Other) / prion
disease (Other)},
cin = {AG Zerr},
ddc = {610},
cid = {I:(DE-2719)1440011-1},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35212083},
doi = {10.1111/ene.15302},
url = {https://pub.dzne.de/record/163435},
}