People with multiple sclerosis (MS) are much less likely to have the molecular markers characteristic of Alzheimer’s than those without the disease, a new study from Washington University School of Medicine in St. Louis has found. A discovery that suggests a new avenue of research for Alzheimer’s treatments, explained Dr. Matthew Brier, assistant professor of neurology and radiology and first author of the study.
“Our findings suggest that some component of the biology of MS, or the genetics of MS patients, may be protective against Alzheimer’s,” Brier said. “If we could identify what aspect of it provides this protection and apply it in a controlled manner, we could develop new therapeutic strategies for Alzheimer’s disease.” The study was published in the journal Annals of Neurology.
The research was the result of a collaboration among Alzheimer’s and MS experts at WashU Medicine and grew out of a suspicion that arose in Brier’s mentor and collaborator, Dr. Anne Cross, after decades of treating patients with MS, an autoimmune disease that attacks the central nervous system. Although many of her patients lived long enough to be at risk for developing Alzheimer’s or had a family history of the neurodegenerative disease, they did not have the disease.
“I noticed that I couldn’t find any of my MS patients who had typical Alzheimer’s,” Cross said. “If they had cognitive problems, I would send them to the memory and aging specialists here at the School of Medicine for an Alzheimer’s evaluation, and those doctors would always tell me, ‘No, this is not due to Alzheimer’s.’” Cognitive decline caused by MS can be confused with Alzheimer’s symptoms; however, Alzheimer’s can be confirmed with blood tests and other biological examinations.
Less likely to accumulate amyloid plaques in the brain
To verify Cross’s observation, the research team used a new FDA-approved blood test developed by researchers at the University of Washington. Known as PrecivityAD2, this test is highly effective at predicting the presence of amyloid plaques in the brain, an indicator of Alzheimer’s that previously could only be confirmed through brain scans or spinal taps.
Brier, Cross and their colleagues recruited 100 MS patients to undergo the blood test, 11 of whom also underwent PET scans at the School of Medicine’s Mallinckrodt Radiology Institute. The results were compared to a control group of 300 people without MS but with similar characteristics in terms of age, genetic risk for Alzheimer’s and cognitive decline. “We found that 50% fewer MS patients had amyloid pathology compared with their control peers, based on this blood test,” Brier said.
This finding supported Cross’s observation that people with MS seemed to be less likely to develop Alzheimer’s. Although it’s not clear how amyloid buildup relates to the cognitive decline typical of Alzheimer’s, plaque buildup is generally considered the first event in the biological cascade that leads to cognitive decline.
“We found that 50% fewer MS patients had amyloid pathology compared to their control peers.”
The researchers also found that the more typical a patient’s MS history was in terms of age of onset, severity and overall disease progression, the less likely they were to accumulate amyloid plaques in the brain compared to those with atypical presentations of MS. This suggests that something about the very nature of MS might be protective against Alzheimer’s, an aspect Brier and Cross plan to investigate further.
MS patients typically experience multiple episodes of the disease over the course of their lives. During these episodes, the immune system attacks the central nervous system, including the brain. It’s possible that this immune activity also reduces amyloid plaques, the researchers said. “Perhaps when the amyloid pathology of Alzheimer’s was developing, MS patients had some degree of inflammation in the brain triggered by their immune responses,” Brier said.
Referring to work by co-author David M. Holtzman, MD, Distinguished Professor of Neurology, Brier noted that activated microglia, which are part of the brain’s immune response in MS, have been shown to be able to clear amyloid from the brain in animal models. Brier and Cross have begun the next steps of this research, both to tease out the possible human genetic components involved and to test the development of amyloid plaques in animal models representing MS.
