Pioneering Research Maps MS Brain Tissues, Unveiling TREM2's Role in Damage and Repair
New research, funded by MS Australia and led by Professor Laura Piccio and Dr. Claire Goldsbury, has mapped cells and molecules within human Multiple Sclerosis (MS) brain tissues. This groundbreaking study utilized advanced technologies to better understand myelin damage and repair processes, particularly in progressive MS. TREM2, a protein found on immune cells, was identified as playing a role in clearing damaged tissue.
This study utilized advanced technologies to better understand myelin damage and repair processes, particularly in progressive MS.
The Crucial Role of TREM2 Protein
A key finding involved the protein TREM2, located on the surface of immune cells such as microglia and macrophages. These cells are involved in clearing damaged tissue, including broken-down myelin, in the brain. The research suggests TREM2 plays a role in MS.
The research suggests TREM2 plays a role in MS, similar to its known function in other conditions where it assists in managing fatty debris.
Advanced Research Methodology
Researchers analyzed donated brain tissue from individuals who had MS, sourced from the MS Australia Brain Bank. They compared various types of MS lesions:
- Active lesions, where damage was occurring.
- Chronic active lesions, which slowly expand over time.
- Repairing (remyelinating) lesions.
- Normal-appearing brain tissue.
The team employed light microscopy, fluorescent tagging, and spatial transcriptomics to measure gene activity in precise anatomical regions within lesions. This revealed intricate cellular interactions and gene expression patterns.
TREM2 Activity and Immune Cell Distribution
TREM2 activity was predominantly observed in active and chronic active lesions, indicating its association with areas of ongoing damage. It was rarely found in normal-appearing tissue.
In damaged areas, TREM2 was present on microglia, macrophages, and perivascular macrophages. These cells were characterized by their accumulation of fats from broken-down myelin. The study also noted the presence of PLIN2, a marker for fat storage units, within nearly all TREM2-positive cells, confirming their active role in storing and processing myelin fats.
Obstacles to Repair
Despite the active clean-up process, the research indicated that within chronic active lesions, TREM2-rich areas also exhibited signals that could inhibit oligodendrocyte precursor cells, which are responsible for producing new myelin. This environment may impede the maturation and movement of these repair cells.
This environment may impede the maturation and movement of these repair cells, potentially explaining why chronic active lesions often persist rather than heal.
Insights from Perilesional White Matter
The study also highlighted the importance of tissue surrounding MS lesions, known as perilesional white matter. This area, which can appear normal on scans, showed activated immune cells, TREM2 activity, and early signs of altered fat processing.
This suggests its involvement in lesion expansion, even before overt damage is visible on scans.
Broader Implications for MS Treatment
These findings contribute significantly to the understanding of fat metabolism and clean-up pathways in MS progression. Future research will explore whether TREM2's clean-up role can be supported without hindering repair, potentially leading to new therapies for slowing MS progression.
The study acknowledges the critical contribution of brain tissue donations from individuals to the MS Australia Brain Bank, which made this vital research possible.