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@ARTICLE{Muqaku:280293,
author = {Muqaku, Besnik and Dorst, Johannes and Wiesenfarth,
Maximilian and Otto, Markus and Ludolph, Albert C and Oeckl,
Patrick},
title = {{P}eptidomic analysis of {CSF} reveals new biomarker
candidates for amyotrophic lateral sclerosis.},
journal = {EMBO molecular medicine},
volume = {17},
number = {8},
issn = {1757-4676},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2025-00948},
pages = {1926 - 1949},
year = {2025},
abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating
neurodegenerative disease, and novel biomarkers are needed.
We applied mass-spectrometry-based peptidomic analysis in
cerebrospinal fluid (CSF) samples of ALS and
non-neurodegenerative control patients (Con) from a
discovery (n = 48) and validation (n = 109) cohort for
biomarker discovery. Systematic selection revealed a panel
of eight novel peptide biomarker candidates for ALS (out of
33,605) derived from seven proteins. In the validation
cohort, NFL, MAP1B, MYL1, and APOC1 peptides were
upregulated, and peptides from CADM3, SCG1, and PENK were
downregulated in ALS compared to Con. The peptides (except
NFL) were not changed in other neurodegenerative diseases,
including Alzheimer´s disease, frontotemporal dementia and
Parkinson´s disease. Combination of all peptides in a
logistic regression model led to an area under the curve
value of $98\%$ for the discrimination of ALS from controls.
Data of the NFL peptide strongly correlated with an
established NFL immunoassay (Ella, r = 0.97). The peptide
biomarker candidates are derived from proteins with
different function, and their determination with our method
provides the opportunity for simultaneous investigation of
key processes in ALS.},
keywords = {Humans / Amyotrophic Lateral Sclerosis: diagnosis /
Amyotrophic Lateral Sclerosis: cerebrospinal fluid /
Amyotrophic Lateral Sclerosis: pathology / Biomarkers:
cerebrospinal fluid / Female / Male / Middle Aged / Aged /
Peptides: cerebrospinal fluid / Cohort Studies / Mass
Spectrometry / Proteomics: methods / Adult / ALS (Other) /
Biomarker (Other) / Muscle (Other) / Neurodegeneration
(Other) / Peptidomics (Other) / Biomarkers (NLM Chemicals) /
Peptides (NLM Chemicals)},
cin = {AG Öckl / Clinical Study Center (Ulm)},
ddc = {610},
cid = {I:(DE-2719)5000073 / I:(DE-2719)5000077},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40681694},
doi = {10.1038/s44321-025-00272-w},
url = {https://pub.dzne.de/record/280293},
}