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@ARTICLE{Braeuer:278027,
author = {Braeuer, Stefan and Weber, Maximilian and Deuschle,
Christian and Julia, Kühlwein and Concha-Marambio, Luis and
Bernhardt, Alexander Maximilian and Kadam, Vaibhavi and
Mengel, David and Ruf, Wolfgang P and Kassubek, Jan and
Schniewind, Inaki and Kuhs, Sandra and Rossi, Marcello and
Parchi, Piero and Levin, Johannes and Danzer, Karin M and
Synofzik, Matthis and Brockmann, Kathrin and Falkenburger,
Björn},
title = {{H}igh {A}greement {A}cross {L}aboratories {B}etween
{D}ifferent {A}lpha-{S}ynuclein {S}eed {A}mplification
{P}rotocols.},
journal = {European journal of neurology},
volume = {32},
number = {4},
issn = {1351-5101},
address = {Oxford [u.a.]},
publisher = {Wiley-Blackwell},
reportid = {DZNE-2025-00537},
pages = {e70165},
year = {2025},
abstract = {Seed amplification assays (SAA) detect alpha-synuclein
(aSYN) pathology in patient biomatrices such as
cerebrospinal fluid (CSF)-potentially even before clinical
manifestations. As CSF-based SAA are approaching broader use
in clinical trials and research, ensuring that different
laboratories obtain the same results becomes increasingly
important.In this cross-laboratory, cross-aSYN-recombinant
substrate and cross-protocol round-robin test, we compared
SAA results from a common set of 38 CSF samples measured
independently in four research laboratories of the German
Center for Neurodegenerative diseases. Three laboratories
(A-C) used an assay protocol adapted from Parchi's group at
ISNB (Bologna, Italy); laboratory D used an assay protocol
adapted from Amprion Inc. Two different manufacturers of
aSYN protein were used as substrates for the SAA
reaction.Qualitative results were identical in at least
three of the four laboratories for 37 out of 38 samples (20
positive, 17 negative). Fleiss Kappa for all four
laboratories was 0.751 (z = 12, p < 0.001). For each
laboratory, agreement with laboratory A was > $92\%.$ For
the number of positive replicates, Fleiss Kappa was 0.45 for
a score of zero positive replicates and 0.42 for a score of
four positive replicates.The qualitative SAA results showed
a high level of agreement across research laboratories, aSYN
monomers, and assay protocols. Small differences between
laboratories were systematic, consistent with the notion
that SAA reports biologically relevant properties. These
results also underline that round-robin tests can be helpful
in assessing and ensuring SAA quality across laboratories.},
keywords = {Humans / alpha-Synuclein: cerebrospinal fluid /
alpha-Synuclein: genetics / Laboratories: standards /
Reproducibility of Results / RT‐QuIC (Other) /
alpha‐synuclein (Other) / method validation (Other) /
proficiency testing (Other) / ring trial (Other) /
alpha-Synuclein (NLM Chemicals)},
cin = {AG Falkenburger / Clinical Research (Munich) / AG Gasser /
AG Danzer / Clinical Study Center (Ulm) / AG Spottke / AG
Levin},
ddc = {610},
cid = {I:(DE-2719)1710012 / I:(DE-2719)1111015 /
I:(DE-2719)1210000 / I:(DE-2719)5000072 / I:(DE-2719)5000077
/ I:(DE-2719)1011103 / I:(DE-2719)1111016},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 352 -
Disease Mechanisms (POF4-352)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40237217},
doi = {10.1111/ene.70165},
url = {https://pub.dzne.de/record/278027},
}