Evidence map›Paper›PMID 41051527›Full record

ArticleJournal of neurology2025

Alpha-internexin as a brain-specific neurodegeneration marker: development and validation of a novel CSF assay.

Francisco J Meda, Anna Dittrich, Ingmar Skoog, Silke Kern, Claire Leckey, Edward J Wild, Ross W Paterson, Gunnar Brinkmalm, Ulf Andreasson, Kaj Blennow and 2 more

Abstract readValidation Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Francisco J MedaDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. francisco.meda@gu.se.ORCID http://orcid.org/0000-0002-3343-7351
Anna DittrichDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Ingmar SkoogDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Silke KernDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Claire LeckeyUK Dementia Research Institute at University College London, London, UK.
Edward J WildUCL Huntington's Disease Centre, Institute of Neurology, University College London, London, UK.
Ross W PatersonUK Dementia Research Institute at University College London, London, UK.
Gunnar BrinkmalmDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Ulf AndreassonDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Kaj BlennowDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
Hlin KvartsbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.

Funding

H2020 Marie Skłodowska-Curie Actions 860197Vetenskapsrådet #2017-00915Vetenskapsrådet #2019-02397Vetenskapsrådet #2022-00732Vetenskapsrådet #2022-01018Vetenskapsrådet #2023-00356
6 · The paper itself

Abstract

backgroundAlpha-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).

methodsMonoclonal 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).

resultsTwo 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.

conclusionsWe 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.

Indexed as

Neurodegenerative DiseasesAdultAgedBiomarkersCohort StudiesEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoassayIntermediate Filament ProteinsMaleMiddle AgedNeurofilament Proteinsalpha-internexinBiomarkersIntermediate Filament Proteinsneurofilament protein LNeurofilament ProteinsAlpha-internexinCerebrospinal fluidImmunoassayNeurofilaments

Identifiers

PMID41051527
PMCPMC12500819

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.