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.

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.

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).

We conclude that CSF AINX, similarly to NfL, is a marker of axonal nerve injury in patients with MS.