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.
