Cerebrospinal fluid alpha-internexin is increased in patients with multiple sclerosis and correlates strongly with neurofilament light protein
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Alpha-internexin (AINX) is an intermediate filament protein predominantly found in the central nervous system (CNS) and is one of the core structural components of the neuronal cytoskeleton, along with the neurofilament triplet proteins. Because AINX is CNS-specific it has the potential to differentiate between peripheral and CNS neuroaxonal injury. METHOD: We measured cerebrospinal fluid (CSF) AINX in patients with multiple sclerosis (MS) and healthy controls (HC) using an in-house AINX Simoa (Single molecule array) assay developed and validated at the Clinical Neurochemistry Laboratory at Sahlgrenska University Hospital, University of Gothenburg. The primary outcome measure was the difference in AINX between patients with MS and HCs. We also calculated correlations with age, sex, MS disease duration, magnetic resonance imaging (MRI) results, CSF biomarkers (cell count, albumin quotient, neurofilament light (NfL), glial fibrillary acidic protein (GFAP), T-Tau, C-X-C motif ligand 13 (CXCL13)), and the influence of MS phenotype, and disease-modifying therapies. RESULTS: We included 34 patients with MS and 8 HCs in the analysis. AINX was detected in all samples (range: 0.16-38.4 ng/L). The median AINX was significantly increased in patients with MS (1.19 ng/L; IQR 0.69-2.34) compared with HCs (0.44 ng/L; IQR 0.36-0.51) (p < 0.001) and correlated strongly with CSF NfL (R = 0.90; p < 0.001). AINX also correlated significantly with expanded disability status scale (EDSS) score (R=-0.4; p = 0.02), number of contrast-enhancing lesions (CELs) (R = 0.6; p < 0.001), CSF cell count (R = 0.6; p < 0.001), and CSF CXCL13 (R = 0.6; p = 0.001). CONCLUSION: We conclude that CSF AINX, similarly to NfL, is a marker of axonal nerve injury in patients with MS.
Institutions: Sahlgrenska University Hospital, Region Västra Götaland, University of Gothenburg, University of Science and Technology of China, University of Wisconsin–Madison, UK Dementia Research Institute, UCL Queen Square Institute of Neurology, University College London, Indian Institute of Science Bangalore
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,500
Funders: Alzheimer's Association, Alzheimer's Drug Discovery Foundation, Familjen Erling-Perssons Stiftelse, Cure Alzheimer's Fund, Stiftelsen för Gamla Tjänarinnor, EU Joint Programme – Neurodegenerative Disease Research, Swedish Foundation for MS Research, National Institute for Health and Care Research, European Commission, Vetenskapsrådet, Stiftelsen Apotekare Hedbergs Fond för Medicinsk Forskning, UK Dementia Research Institute, Olav Thon Stiftelsen, Horizon 2020 Framework Programme, H2020 Marie Skłodowska-Curie Actions
Awards: G1149115962, G1343867371, G1628922872, G2015123609, G2172110011, G2282995069, G2434909840, G2543812357, G2777547358, G2983944509, G3448198908, G3561172447, G3902407205, G4206453169, G4207470147, G4260843567, G444530504, G4725210227, G5350608752, G5883150156, Multi-omics Interdisciplinary Research Integration to Address DEmentia diagnosis, G6174583484, G6396167455, G6965221316, G7203141297, G7402606106, G7919073335, G8447322580, G8893056158, G936408231
OpenAlex ID: W4415269340