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@ARTICLE{Wilke:153278,
author = {Wilke, Carlo and Haas, Eva and Reetz, Kathrin and Faber,
Jennifer and Garcia‐Moreno, Hector and Santana, Magda M
and Warrenburg, Bart and Hengel, Holger and Lima, Manuela
and Filla, Alessandro and Durr, Alexandra and Melegh, Bela
and Masciullo, Marcella and Infante, Jon and Giunti, Paola
and Neumann, Manuela and Vries, Jeroen and Pereira de
Almeida, Luis and Rakowicz, Maria and Jacobi, Heike and
Schüle, Rebecca and Kaeser, Stephan A and Kuhle, Jens and
Klockgether, Thomas and Schöls, Ludger and Barro, Christian
and Hübener‐Schmid, Jeannette and Synofzik, Matthis and
Deuschle, Christian and Stransky, Elke and Brockmann,
Kathrin and Schulz, Jörg B and Baliko, Laszlo and Gaalen,
Judith and Raposo, Mafalda and Jeromin, Andreas},
title = {{N}eurofilaments in spinocerebellar ataxia type 3: blood
biomarkers at the preataxic and ataxic stage in humans and
mice},
journal = {EMBO molecular medicine},
volume = {12},
number = {7},
issn = {1757-4684},
address = {Heidelberg},
publisher = {EMBO Press},
reportid = {DZNE-2020-01275},
pages = {e11803},
year = {2020},
abstract = {With molecular treatments coming into reach for
spinocerebellar ataxia type 3 (SCA3), easily accessible,
cross‐species validated biomarkers for human and
preclinical trials are warranted, particularly for the
preataxic disease stage. We assessed serum levels of
neurofilament light (NfL) and phosphorylated neurofilament
heavy (pNfH) in ataxic and preataxic subjects of two
independent multicentric SCA3 cohorts and in a SCA3
knock‐in mouse model. Ataxic SCA3 subjects showed
increased levels of both NfL and pNfH. In preataxic
subjects, NfL levels increased with proximity to the
individual expected onset of ataxia, with significant NfL
elevations already 7.5 years before onset. Cross‐sectional
NfL levels correlated with both disease severity and
longitudinal disease progression. Blood NfL and pNfH
increases in human SCA3 were each paralleled by similar
changes in SCA3 knock‐in mice, here also starting already
at the presymptomatic stage, closely following ataxin‐3
aggregation and preceding Purkinje cell loss in the brain.
Blood neurofilaments, particularly NfL, might thus provide
easily accessible, cross‐species validated biomarkers in
both ataxic and preataxic SCA3, associated with earliest
neuropathological changes, and serve as progression,
proximity‐to‐onset and, potentially,
treatment‐response markers in both human and preclinical
SCA3 trials.},
keywords = {Animals / Biomarkers: blood / Cross-Sectional Studies /
Female / Humans / Intermediate Filaments: chemistry /
Machado-Joseph Disease: blood / Male / Mice / Prodromal
Symptoms / Severity of Illness Index},
cin = {Core ICRU / Patient Studies Bonn / AG Gasser / AG Neumann /
AG Maetzler / AG Jucker / AG Jessen / AG Schöls},
ddc = {610},
cid = {I:(DE-2719)1240005 / I:(DE-2719)1011101 /
I:(DE-2719)1210000 / I:(DE-2719)1210003 / I:(DE-2719)5000024
/ I:(DE-2719)1210001 / I:(DE-2719)1011102 /
I:(DE-2719)5000005},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342) / 345
- Population Studies and Genetics (POF3-345) / 344 -
Clinical and Health Care Research (POF3-344)},
pid = {G:(DE-HGF)POF3-342 / G:(DE-HGF)POF3-345 /
G:(DE-HGF)POF3-344},
experiment = {EXP:(DE-2719)ESMI-20140101},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC7338806},
pubmed = {pmid:32510847},
doi = {10.15252/emmm.201911803},
url = {https://pub.dzne.de/record/153278},
}