Daan van der Vliet stood in the lab at the Netherlands Institute for Neuroscience with a puzzle that has haunted MS researchers for decades: Why does one patient's disease remain mild for years while another's spirals into rapid paralysis? His team may have found an answer hidden inside the brain's own immune cells—and it changes how scientists think about the disease.
Multiple sclerosis unfolds differently in every person. Some patients live for decades with manageable symptoms like walking difficulties or vision problems. Others become severely disabled while still young. This unpredictable progression has long mystified researchers, but van der Vliet's discovery published in Nature Neuroscience offers a new lens: abnormal immune cells overloaded with fat may mark those heading toward severe disease.
The cells in question are microglia, the brain's cleanup crew. Normally, these immune cells remove waste and repair damage. But in MS patients with rapidly progressive disease, something goes wrong. Van der Vliet and his colleagues at Leiden University and Utrecht University analyzed brain tissue from 28 deceased MS patients and found large numbers of abnormal microglia stuffed with fat droplets—cells researchers call "foamy microglia." The finding was striking: patients with abundant foamy microglia showed a more severe disease course far more frequently than those without them.
The mechanism, van der Vliet explains, is almost tragic. "These cells are probably trying to do something good: clearing up damage. But they become overloaded, so to speak. As a result, they can no longer effectively contribute to repair." In MS, the fatty myelin coating nerve fibers breaks down, creating a massive cleanup job. The microglia absorb damaged myelin trying to help, but their waste-processing system gets overwhelmed. Instead of healing, the cells themselves become part of the problem.
The discovery upends how scientists understand MS progression. For years, experts assumed inflammation itself drove disease severity. Van der Vliet's work suggests something more nuanced: the immune system's attempt to repair becomes corrupted, worsening inflammation and blocking recovery. Brain inflammations containing foamy microglia show distinctly different molecular profiles, including specific fats linked to chronic inflammatory responses—a signature of failure, not help.
The research was only possible because of precision. The team combined advanced techniques examining gene activity, proteins, and fats within the same MS lesions simultaneously, then mapped their findings onto carefully classified brain tissue from the Netherlands Brain Bank, which has systematized brain pathology for years. As van der Vliet notes, cutting-edge technology means little without connection to human pathology—and this work proved that marriage invaluable.
The implications ripple forward. Researchers have found hints that fats associated with foamy microglia appear measurable in patients' cerebrospinal fluid, raising the possibility of future biomarkers that could flag which patients face rapid decline early—and guide doctors toward personalized treatments. Van der Vliet envisions a day when such tests help identify at-risk patients before symptoms accelerate, allowing interventions tailored to each person's disease course. New medicines already in development target fat metabolism and chronic lesions, pathways van der Vliet's discovery now illuminates.
For MS patients living with relentless uncertainty, this research from Amsterdam offers something precious: the beginning of an answer to why their disease behaves differently, and a path toward treatments designed for their individual progression.