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000281734 0247_ $$2doi$$a10.1016/j.ebiom.2025.105930
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000281734 1001_ $$aFazeli, Badrieh$$b0
000281734 245__ $$aComparative analysis of cerebrospinal fluid neurofilament medium, light and heavy chain in neurodegenerative diseases using an in-house assay for the detection of neurofilament medium chain.
000281734 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2025
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000281734 520__ $$aNeurofilaments are key axonal proteins, with neurofilament light (NfL) and heavy (NfH) chain recognised as promising biomarkers for neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). However, neurofilament medium chain (NfM) remained previously underexplored due to a lack of quantitative assays. In this study, we developed a sensitive immunoassay to measure NfM in cerebrospinal fluid (CSF) and analysed its levels in ALS, Alzheimer's disease (AD), frontotemporal dementia (FTD), and Lewy body dementia (LBD). Correlations among neurofilaments and their diagnostic performance were also evaluated.In this study CSF levels of three neurofilament proteins were measured in 305 participants, including patients with ALS (n = 91), AD (n = 59), FTD (n = 38), LBD (n = 18), non-neurodegenerative controls (CTRL, n = 51), and 48 individuals initially evaluated for ALS but ultimately diagnosed with other conditions (CTRL.DD). NfM levels were quantified using a homemade sandwich ELISA, while NfL and NfH were measured using commercialised Ella cartridges.All three neurofilaments were significantly elevated in ALS compared to CTRL and CTRL.DD groups (p < 0.0001 for both), with NfM and NfL also increased in FTD (p < 0.0001 for both) and AD (NfM, p < 0.0001; NfL, p = 0.0001) compared to CTRL. NfH demonstrated the greatest distinction between ALS and FTD (p < 0.0001). Strong correlations were observed among neurofilament subunits, particularly between NfM and NfL (r = 0.93, 95% CI: 0.91-0.94, p < 0.0001). All neurofilaments effectively distinguished ALS from CTRL and CTRL.DD, with AUC values ranging from 0.92 to 0.99. NfM and NfL showed high accuracy in differentiating AD (NfM, AUC: 0.91; NfL, AUC: 0.89) and FTD (NfM, AUC: 0.91; NfL, AUC: 0.92) from CTRL, while NfH best separated ALS from FTD (AUC: 0.96).This study provides a quantitative comparison of NfM with NfL and NfH in a neurodegenerative cohort, highlighting its potential diagnostic value. Further research with larger cohorts, longitudinal studies, and investigations into neurofilament distribution in different compartments is needed to clarify the distinct roles of NfM, NfL, and NfH in the diagnosis and treatment of neurological diseases.The present study was supported by the Else Kroener-Fresenius Foundation (2024-EKEA.126) and Chemische Fabrik Karl Bucher GmbH.
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000281734 650_7 $$2Other$$aAlzheimer's diseases
000281734 650_7 $$2Other$$aAmyotrophic lateral sclerosis
000281734 650_7 $$2Other$$aELISA
000281734 650_7 $$2Other$$aFluid biomarkers
000281734 650_7 $$2Other$$aNeurofilament medium chain
000281734 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000281734 650_7 $$2NLM Chemicals$$aBiomarkers
000281734 650_7 $$2NLM Chemicals$$aneurofilament protein L
000281734 650_7 $$0111365-29-8$$2NLM Chemicals$$aneurofilament protein M
000281734 650_7 $$0108688-71-7$$2NLM Chemicals$$aneurofilament protein H
000281734 650_2 $$2MeSH$$aHumans
000281734 650_2 $$2MeSH$$aNeurofilament Proteins: cerebrospinal fluid
000281734 650_2 $$2MeSH$$aMale
000281734 650_2 $$2MeSH$$aFemale
000281734 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000281734 650_2 $$2MeSH$$aNeurodegenerative Diseases: cerebrospinal fluid
000281734 650_2 $$2MeSH$$aNeurodegenerative Diseases: diagnosis
000281734 650_2 $$2MeSH$$aAged
000281734 650_2 $$2MeSH$$aMiddle Aged
000281734 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: cerebrospinal fluid
000281734 650_2 $$2MeSH$$aAmyotrophic Lateral Sclerosis: diagnosis
000281734 650_2 $$2MeSH$$aROC Curve
000281734 650_2 $$2MeSH$$aAged, 80 and over
000281734 650_2 $$2MeSH$$aFrontotemporal Dementia: cerebrospinal fluid
000281734 650_2 $$2MeSH$$aFrontotemporal Dementia: diagnosis
000281734 7001_ $$aBotzenhardt, Sara$$b1
000281734 7001_ $$aBachhuber, Franziska$$b2
000281734 7001_ $$0P:(DE-2719)9001969$$aKlassen, Paula Cynthia$$b3
000281734 7001_ $$0P:(DE-2719)9001084$$aKlose, Veronika$$b4$$udzne
000281734 7001_ $$0P:(DE-2719)9001951$$aDorst, Johannes$$b5$$udzne
000281734 7001_ $$aWiesenfarth, Maximilian$$b6
000281734 7001_ $$aUzelac, Zeljko$$b7
000281734 7001_ $$0P:(DE-2719)9001441$$aJesse, Sarah$$b8$$udzne
000281734 7001_ $$0P:(DE-2719)9002137$$aBrenner, David$$b9$$udzne
000281734 7001_ $$aAnderl-Straub, Sarah$$b10
000281734 7001_ $$0P:(DE-2719)2812633$$aLudolph, Albert$$b11$$udzne
000281734 7001_ $$aOtto, Markus$$b12
000281734 7001_ $$aWeishaupt, Jochen$$b13
000281734 7001_ $$0P:(DE-2719)9002007$$aTumani, Hayrettin$$b14$$udzne
000281734 7001_ $$0P:(DE-2719)9002026$$aHalbgebauer, Steffen$$b15$$eLast author$$udzne
000281734 773__ $$0PERI:(DE-600)2799017-5$$a10.1016/j.ebiom.2025.105930$$gVol. 120, p. 105930 -$$p105930$$tEBioMedicine$$v120$$x2352-3964$$y2025
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