Objective:

To investigate the role of lipid-filled immune cells in the progression of multiple sclerosis (MS) lesions.

Approach:

• Study Design: Analysis of postmortem brain tissue from patients with secondary progressive MS using molecular and histological techniques.

Key Findings:

• Lesions with 'foamy' microglia, which are lipid-filled immune cells, were linked to faster disease progression.
• Patients with more foamy lesions reached disability milestones sooner than those with fewer.
• Remyelinated lesions were associated with slower disease progression.
• Foamy microglia exhibited abnormal lipid metabolism and impaired waste processing.
• Increased immune activity was observed in chronic lesions, distinct from typical inflammation in active MS lesions.
• Monoacylglycerol lipase (MAGL) was identified as a potential therapeutic target.
• Lipid molecules known as oxylipins in cerebrospinal fluid correlated with the number of foamy lesions.

Interpretation:

Chronic active lesions in MS represent a distinct disease process, and lipid-filled microglia and related markers may improve diagnosis and monitoring.

Limitations:

• The study is based on postmortem tissue, providing a static snapshot rather than dynamic changes over time.
• The clinical value of identified biomarkers needs confirmation through further studies in living patients.

Conclusion:

Combining histopathology with molecular profiling may enhance understanding of progressive MS.

Sources:

• Nature Neuroscience