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000280293 1001_ $$0P:(DE-2719)9001534$$aMuqaku, Besnik$$b0$$eFirst author$$udzne
000280293 245__ $$aPeptidomic analysis of CSF reveals new biomarker candidates for amyotrophic lateral sclerosis.
000280293 260__ $$a[London]$$bNature Publishing Group UK$$c2025
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000280293 520__ $$aAmyotrophic 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.
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000280293 650_7 $$2Other$$aALS
000280293 650_7 $$2Other$$aBiomarker
000280293 650_7 $$2Other$$aMuscle
000280293 650_7 $$2Other$$aNeurodegeneration
000280293 650_7 $$2Other$$aPeptidomics
000280293 650_7 $$2NLM Chemicals$$aBiomarkers
000280293 650_7 $$2NLM Chemicals$$aPeptides
000280293 650_2 $$2MeSH$$aHumans
000280293 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: diagnosis
000280293 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: cerebrospinal fluid
000280293 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: pathology
000280293 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000280293 650_2 $$2MeSH$$aFemale
000280293 650_2 $$2MeSH$$aMale
000280293 650_2 $$2MeSH$$aMiddle Aged
000280293 650_2 $$2MeSH$$aAged
000280293 650_2 $$2MeSH$$aPeptides: cerebrospinal fluid
000280293 650_2 $$2MeSH$$aCohort Studies
000280293 650_2 $$2MeSH$$aMass Spectrometry
000280293 650_2 $$2MeSH$$aProteomics: methods
000280293 650_2 $$2MeSH$$aAdult
000280293 7001_ $$0P:(DE-2719)9001951$$aDorst, Johannes$$b1$$udzne
000280293 7001_ $$0P:(DE-HGF)0$$aWiesenfarth, Maximilian$$b2
000280293 7001_ $$00000-0003-4273-4267$$aOtto, Markus$$b3
000280293 7001_ $$0P:(DE-2719)2812633$$aLudolph, Albert C$$b4$$udzne
000280293 7001_ $$0P:(DE-2719)9001560$$aOeckl, Patrick$$b5$$eLast author
000280293 773__ $$0PERI:(DE-600)2485479-7$$a10.1038/s44321-025-00272-w$$gVol. 17, no. 8, p. 1926 - 1949$$n8$$p1926 - 1949$$tEMBO molecular medicine$$v17$$x1757-4676$$y2025
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