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Updated: Jun 5, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Tyro3 and Gas6 are associated with white matter and myelin integrity in multiple sclerosis
Igal Rosenstein1,2, Lenka Novakova3,4, Hlin Kvartsberg5,6
1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Blå Stråket 7, 413 45, Gothenburg, Sweden. igal.rosenstein@vgregion.se.
Background:
The Gas6/TAM (Tyro3, Axl, and Mer) receptor system has been implicated in demyelination and delayed remyelination in experimental animal models, but data in humans are scarce. We aimed to investigate the role of Gas6/TAM in neurodegenerative processes in multiple sclerosis (MS).
Methods:
From a prospective 5-year follow-up study, soluble Gas6/TAM biomarkers were analyzed in cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assay (ELISA) at baseline in patients with relapsing-remitting MS (RRMS) (n = 40), progressive MS (PMS) (n = 20), and healthy controls (HC) (n = 25). Brain volumes, including myelin content (MyC) and white matter (WM) were measured by synthetic magnetic resonance imaging at baseline, 12 months, and 60-month follow-up. Associations with brain volume changes were investigated in multivariable linear regression models. Gas6/TAM concentrations were also determined at 12 months follow-up in RRMS to assess treatment response.
Results:
Baseline concentrations of Tyro3, Axl, and Gas6 were significantly higher in PMS vs. RRMS and HC. Mer was higher in PMS vs. HC. Tyro3 and Gas6 were associated with reduced WM (β = 25.5, 95% confidence interval [CI] [6.11-44.96, p = 0.012; β = 11.4, 95% CI [0.42-22.4], p = 0.042, respectively) and MyC (β = 7.95, 95%CI [1.84-14.07], p = 0.012; β = 4.4, 95%CI [1.04-7.75], p = 0.012 respectively) at 60 months. Patients with evidence of remyelination at last follow-up had lower baseline soluble Tyro3 (p = 0.033) and Gas6 (p = 0.014). Except Mer, Gas6/TAM concentrations did not change with treatment in RRMS.
Discussion:
Our data indicate a potential role for the Gas6/TAM receptor system in neurodegenerative processes influencing demyelination and ineffective remyelination.
Insights
The Gas6/TAM receptor system is linked to neurodegeneration in multiple sclerosis (MS). Higher levels correlate with reduced white matter and myelin, suggesting a role in ineffective remyelination.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- The Gas6/TAM receptor system is implicated in demyelination and remyelination processes.
- Human data on Gas6/TAM's role in multiple sclerosis (MS) neurodegeneration are limited.
Purpose of the Study:
- To investigate the role of the Gas6/TAM receptor system in neurodegenerative processes in MS.
- To analyze Gas6/TAM biomarkers in cerebrospinal fluid (CSF) and their association with brain changes.
Main Methods:
- Prospective 5-year follow-up study analyzing soluble Gas6/TAM biomarkers in CSF via ELISA.
- Assessed brain volumes, myelin content (MyC), and white matter (WM) using synthetic MRI.
- Multivariable linear regression models investigated associations with brain volume changes.
Main Results:
- Significantly higher baseline Tyro3, Axl, and Gas6 levels were observed in progressive MS (PMS) patients compared to relapsing-remitting MS (RRMS) and healthy controls (HC).
- Elevated Tyro3 and Gas6 were associated with reduced white matter and myelin content at 60 months.
- Patients showing remyelination had lower baseline Tyro3 and Gas6 levels.
Conclusions:
- The Gas6/TAM receptor system may play a role in neurodegenerative processes in MS.
- Findings suggest involvement in demyelination and impaired remyelination.
- Further research is warranted to explore therapeutic potential.
