Rot, U;
Sandelius, Å;
Emeršič, A;
Zetterberg, H;
Blennow, K;
(2018)
Cerebrospinal fluid GAP-43 in early multiple sclerosis.
Multiple Sclerosis Journal - Experimental, Translational and Clinical
, 4
(3)
10.1177/2055217318792931.
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Abstract
Background/Objective: Novel biomarkers identifying and predicting disease activity in multiple sclerosis (MS) would be valuable for primary diagnosis and as outcome measures for monitoring therapeutic effects in clinical trials. Axonal loss is present from the earliest stages of MS and correlates with disability measures. Growth-associated protein 43 (GAP-43) is a presynaptic protein with induced expression during axonal growth. We hypothesized this protein could serve as a biomarker of axonal regeneration capacity in MS. Methods: We developed a novel GAP-43 enzyme-linked immunosorbent assay for quantification in cerebrospinal fluid (CSF) and measured GAP-43 levels in 71 patients with clinically isolated syndrome, 139 MS patients and 51 controls. Results: GAP-43 concentrations were similar in patients and controls. Nevertheless, GAP-43 levels were higher in patients with >10 T2-magnetic resonance imaging (MRI) lesions (p = 0.005). CSF GAP-43 concentrations correlated with CSF mononuclear cell counts (p = 0.031) and were inversely correlated with patient age (p = 0.038) with a trend for higher CSF GAP-43 concentrations in patients with gadolinium-enhancing MRI lesions and positive CSF oligoclonal immunoglobulin G status. Conclusion: Our results suggest that axonal regeneration capacity is relatively preserved in early MS. CSF GAP-43 concentration is positively associated with markers of inflammation, suggesting possible inflammatory-driven expression of this growth-associated protein in early MS.
| Type: | Article |
|---|---|
| Title: | Cerebrospinal fluid GAP-43 in early multiple sclerosis |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1177/2055217318792931 |
| Publisher version: | https://doi.org/10.1177/2055217318792931 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Multiple sclerosis, axonal loss, axonal regeneration, biomarkers, cerebrospinal fluid, growth-associated protein 43 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10064009 |
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