Multiple sclerosis (MS) is a disease in which the immune system attacks the protective sheath, called myelin, that covers nerves in the brain and spinal cord (central nervous system; CNS). Myelin damage is called “demyelination”. This disrupts communication between the brain/spinal cord and the rest of the body. The CNS can generate new myelin (called “remyelination”) after damage, but for unknown reasons, remyelination fails or is incomplete in MS. We do know that efficient removal of myelin debris from the area after demyelination is essential before remyelination can occur.
In the CNS, a specific cell type, called microglia, can clear out myelin debris after damage. In MS lesions, one of their functions is to pick up, digest and clear myelin debris. How microglia are activated to clear myelin is not known.
Associate Professor Laura Piccio has been studying the role of TREM2, a protein on the surface of microglia, in the clearance of myelin debris and remyelination. The team’s preliminary results suggest that TREM2 plays a key function in these processes and that the activation of TREM2 could enhance clearance of myelin debris and remyelination.
The goal of this study is to investigate the molecular mechanisms supporting remyelination in the CNS with a specific focus on the effects of activating TREM2.
Using brain and spinal cord tissue, the team found that TREM2 is present on both microglia and macrophages that enter the CNS during MS. They observed that the number of cells expressing TREM2 increased in areas of inflammation. Some of these TREM2-positive cells were actively involved in clearing away myelin and lipid debris, an important step that may support the process of remyelination. This is the first time TREM2 has been characterised in human tissue in MS research.
In collaboration with colleagues at Ohio State University, the researchers also examined patterns of gene activity in these areas of inflammation. Their findings confirmed that these regions contain large numbers of microglia and macrophages, and identified a relationship between TREM2 and CD68, a marker associated with cells that remove debris. Together, these findings improve our understanding of how immune cells respond to damage in MS and may help identify new approaches to support repair within the central nervous system.
Aguirre Candia, Y., Aladyeva, E., Boyden, J. W., Bollman, B., Rogerson-Wood, L., Davies, S., Affleck, A. J., Buckland, M. E., Harari, O., Piccio, L., & Goldsbury, C. (2026). Spatial characterisation of TREM2 expression in actively demyelinating multiple sclerosis lesions supports its key roles in lipid metabolic pathways. Acta Neuropathologica Communications, 14(1), 66. https://doi.org/10.1186/s40478-026-02241-x
Updated 31 March 2026
$250,000
2023
4 years
Current project
