A joint investigation led by specialists in Alzheimer’s disease and multiple sclerosis (MS) provides insights indicating that individuals with MS are less prone to developing amyloid plaques, which are typically associated with Alzheimer’s, compared to those without MS.
New research from Washington University School of Medicine in St. Louis reveals that people with multiple sclerosis (MS) are significantly less likely to exhibit the molecular features linked to Alzheimer’s disease than those who do not have this condition.
This finding opens up new research possibilities for potential Alzheimer’s treatments, according to Matthew Brier, MD PhD, who is an assistant professor of neurology and radiology as well as the primary author of the study.
“What we discovered suggests that there may be certain biological or genetic factors in MS patients that protect them against Alzheimer’s disease,” Brier remarked. “Identifying these protective aspects could lead to new therapeutic strategies for combating Alzheimer’s.”
The research, which showcases how real-world clinical observations can shape scientific inquiries, has been published in the Annals of Neurology.
Initiated by experts at WashU Medicine in Alzheimer’s and MS, the study grew from long-held suspicions of Brier’s mentor and collaborator, Anne Cross, MD, who has treated numerous MS patients. She noted that although her patients live long enough to be at risk for Alzheimer’s or have a familial tendency for the disease, they often do not develop it.
“In my experience, I had not encountered a single MS patient who exhibited classic Alzheimer’s disease symptoms,” Cross, chair of the Manny and Rosalyn Rosenthal and Dr. John Trotter MS Center in Neuroimmunology, said. “If my patients had cognitive difficulties, I would refer them for an Alzheimer’s assessment, and the specialists always concluded there was no evidence of Alzheimer’s.”
The cognitive difficulties resulting from MS can often mimic Alzheimer’s symptoms; however, Alzheimer’s can be formally diagnosed through blood and other biological tests.
To validate Cross’s observations, the research team employed an FDA-approved blood test, developed by WashU Medicine researchers, called PrecivityAD2. This blood test is particularly effective in predicting the presence of amyloid plaques in the brain—these plaques are an Alzheimer’s indicator, which were previously confirmed only through brain scans or spinal taps.
Brier, Cross, and their team tested 100 MS patients, 11 of whom also received PET scans at WashU Medicine’s Mallinckrodt Institute of Radiology. Their outcomes were compared with a control group of 300 individuals without MS who were matched for age, genetic predisposition to Alzheimer’s, and cognitive decline.
“Our analysis indicated that MS patients had 50% fewer occurrences of amyloid pathology compared to their matched peers based on the blood test,” Brier stated. This confirmed Cross’s earlier observation that Alzheimer’s appeared less likely to occur in those with MS. While the precise connection between amyloid accumulation and typical Alzheimer’s cognitive impairment remains unclear, it is commonly understood that the formation of plaques initiates a biological process leading to cognitive decline.
The researchers discovered that the more standard the MS patient’s history is—with respect to age of start, severity, and overall disease course—the less likely they are to show signs of amyloid plaque accumulation, in contrast to those with more atypical MS presentations. This suggests that inherent characteristics of MS may offer some protection against Alzheimer’s disease, a hypothesis Brier and Cross intend to further explore.
Patients with MS typically experience multiple flare-ups throughout their lives. During these episodes, the immune system targets the central nervous system, including the brain. It is possible that this immune response may also help in reducing amyloid plaque levels, according to the researchers.
“It’s conceivable that while amyloid pathology associated with Alzheimer’s disease was forming, patients with MS experienced some level of inflammation in their brains due to their immune responses,” Brier explained. He referenced work by co-author David M. Holtzman, MD, highlighting that activated microglia, a component of the brain’s immune response in MS, have demonstrated the capability to eliminate amyloid from the brains in animal studies.
Brier and Cross are now proceeding with further research to explore the genetic factors involved in humans and to examine amyloid plaque development in animal models that simulate MS.
Several of the co-authors of this study are linked to C2N Diagnostics, a startup at WashU Medicine that assisted in the study. The PrecivityAD2 test is founded on technology that was licensed to C2N by the university.
