Researchers from the Netherlands Institute for Neuroscience, Leiden University and Utrecht University found a new clue about why multiple sclerosis (MS) can become very severe. By looking at brain tissue from people whose MS got worse quickly, they saw many immune cells that were packed with fat droplets. These cells are called "foamy microglia" and may help doctors predict fast disease progression.
MS harms myelin, the fatty coating that protects nerve fibers in the brain and spinal cord. When myelin breaks down, people may have trouble walking, seeing, or moving their arms. Some patients stay mild for years, while others become disabled early. Scientists want to know why.
Microglia are the brain’s clean‑up crew. They eat debris and help repair tissue. In MS, many microglia fill up with fat from damaged myelin and look foamy. The researchers noticed that patients with many foamy microglia often had a worse disease course.
When Clean‑Up Cells Get Overloaded
Normally, microglia keep the brain healthy by clearing out junk. In MS, they may take in so much broken myelin that they cannot process it any more. "They are trying to help, but they become overloaded and stop working properly," explained lead researcher Daan van der Vliet.
The study also showed that brain areas with foamy microglia contain special fats that keep inflammation alive for a long time.
A More Complex View of MS
Inflammation has long been seen as the main driver of MS. The new findings suggest the story is more complicated. The foamy microglia try to clean up damage, but when they fail, they add to inflammation and block recovery.
How the Scientists Looked at the Brain
The team examined brain tissue from 28 donors who had MS. They used several modern tools at once to study gene activity, proteins and fats inside each lesion. This gave a detailed picture of what is happening inside the brain.
"We have amazing technology to map the brain, but it only makes sense when we connect it to real tissue findings," said Van der Vliet.
Future Biomarkers and Personalised Treatment
The fatty molecules linked to foamy microglia were also found in spinal fluid. If later studies confirm this, doctors could use them as biomarkers to spot patients who may worsen quickly.
These insights match current efforts to create medicines that target fat metabolism and stop chronic MS lesions from growing. Some of those experimental drugs are already being tested with partner companies.
The research was funded by two Gravitation programs: the Institute for Chemical Immunology (ICI) and the Institute for Chemical NeuroScience (iCNS).