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Updated: Jan 15, 2026
A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Alpha-internexin as a brain-specific neurodegeneration marker: development and validation of a novel CSF assay
Francisco J Meda1, Anna Dittrich2,3,4, Ingmar Skoog2,4
1Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. francisco.meda@gu.se.
Background:
Alpha-internexin (AINX) is a type IV intermediate filament alongside the neurofilament triplet proteins and periferin. Despite its homologies, the key difference is that AINX is central nervous system-specific. The purpose of this study was to develop an immunoassay for cerebrospinal fluid (CSF) AINX, quantify it in patients with neurodegenerative diseases, and compare its diagnostic performance with neurofilament light (NfL).
Methods:
Monoclonal antibodies were generated and characterized by immunoprecipitation followed by mass spectrometry and ELISA, for specificity to the target analyte and cross-reactivity. Single molecule array (Simoa) technology was the selected platform for assay development. The assay was validated according to pre-established parameters and AINX performance as a biomarker was tested in two independent cohorts (Gothenburg and University College London).
Results:
Two highly specific antibodies were generated (B15 and Ina1) and used to develop a robust assay in all analytical validation parameters tested. The quantitative range of the assay was 0.137-140 pg/mL. In the Gothenburg cohort, AINX and NfL showed similar diagnostic performance, but the correlation between biomarkers was diagnosis dependent. In the University College London cohort, AINX and NfL showed similar trends across the different neurodegenerative diseases, with strong correlation between markers.
Conclusions:
We developed a highly sensitive and specific immunoassay for AINX in CSF. AINX showed similar diagnostic performance and high correlation with CSF NfL. Further research should focus on describing its role in specific disorders, as well as evaluate its potential as a blood-based biomarker.
