TY  - JOUR
AU  - Fazeli, Badrieh
AU  - Botzenhardt, Sara
AU  - Bachhuber, Franziska
AU  - Klassen, Paula Cynthia
AU  - Klose, Veronika
AU  - Dorst, Johannes
AU  - Wiesenfarth, Maximilian
AU  - Uzelac, Zeljko
AU  - Jesse, Sarah
AU  - Brenner, David
AU  - Anderl-Straub, Sarah
AU  - Ludolph, Albert
AU  - Otto, Markus
AU  - Weishaupt, Jochen
AU  - Tumani, Hayrettin
AU  - Halbgebauer, Steffen
TI  - Comparative 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.
JO  - EBioMedicine
VL  - 120
SN  - 2352-3964
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2025-01167
SP  - 105930
PY  - 2025
AB  - Neurofilaments 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
KW  - Humans
KW  - Neurofilament Proteins: cerebrospinal fluid
KW  - Male
KW  - Female
KW  - Biomarkers: cerebrospinal fluid
KW  - Neurodegenerative Diseases: cerebrospinal fluid
KW  - Neurodegenerative Diseases: diagnosis
KW  - Aged
KW  - Middle Aged
KW  - Amyotrophic Lateral Sclerosis: cerebrospinal fluid
KW  - Amyotrophic Lateral Sclerosis: diagnosis
KW  - ROC Curve
KW  - Aged, 80 and over
KW  - Frontotemporal Dementia: cerebrospinal fluid
KW  - Frontotemporal Dementia: diagnosis
KW  - Alzheimer's diseases (Other)
KW  - Amyotrophic lateral sclerosis (Other)
KW  - ELISA (Other)
KW  - Fluid biomarkers (Other)
KW  - Neurofilament medium chain (Other)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - Biomarkers (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
KW  - neurofilament protein M (NLM Chemicals)
KW  - neurofilament protein H (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40974909
C2  - pmc:PMC12481134
DO  - DOI:10.1016/j.ebiom.2025.105930
UR  - https://pub.dzne.de/record/281734
ER  -