Diversity in MS Research and Clinical Trials
Close
Reposted with permission from MS News Today
20 Sep 2024 | ~3:01 Engagement Time
People with multiple sclerosis (MS) are about half as likely as those without the disease to have signs of the amyloid-beta plaques in the brain that are a hallmark of Alzheimer’s disease, according to a study in the U.S.
“Our findings imply that some component of the biology of multiple sclerosis, or the genetics of MS patients, is protective against Alzheimer’s disease,” Matthew Brier, MD, PhD, the study’s first author and an assistant professor at Washington University School of Medicine in St. Louis, said in a university news story.
The reason behind the link remains unknown.
The study, “Unexpected Low Rate of Amyloid-[beta] Pathology in Multiple Sclerosis Patients,” was published as a brief communication in the Annals of Neurology.
In MS, the immune system mistakenly attacks myelin, the fatty sheath around nerve fibers in the brain and spinal cord, causing symptoms such as muscle weakness, poor vision, and numbness. It also can cause cognitive problems, including memory loss. These symptoms could be confused with symptoms of Alzheimer’s, the most common cause of dementia.
Anne Cross, MD, an MS specialist at the university, found it interesting that her patients rarely developed Alzheimer’s, even though they were old enough to be at risk for it.
“I noticed that I couldn’t find a single MS patient of mine who had typical Alzheimer’s disease,” Cross said. “If they had cognitive problems, I would send them to the memory and aging specialists here at WashU Medicine for an Alzheimer’s assessment, and those doctors would always come back and tell me, ‘No, this is not due to Alzheimer’s disease.’”
Cross teamed up with Brier and other researchers to study whether people with MS have the same risk of developing Alzheimer’s as those without the condition.
The researchers used PrecivityAD2, a blood test from C2N Diagnostics that’s approved in the U.S. to predict the presence of amyloid-beta plaques in the brain. These toxic protein clumps are a hallmark and a driver of Alzheimer’s-associated neurodegeneration.
PrecivityAD2 looks for signs of Alzheimer’s in the blood by measuring three key indicators: the ratio of two forms of a protein called tau, the ratio of two forms of amyloid-beta protein, and a score called the amyloid probability score (APS2), which predicts the likelihood of having Alzheimer’s.
The team recruited 100 people older than 60 with MS and compared their PrecivityAD2 results with those of 300 sex- and age-matched adults without MS. These controls, who could have either normal or impaired cognitive function, had similar rates of an Alzheimer’s genetic risk factor, called APOE, to MS patients.
Results showed that people with MS were about half as likely to have signs of Alzheimer’s as controls. For example, the proportion of people with a positive APS2 score was more than twice as high among those without MS (15.3% vs. 7.1%), meaning they were more likely to have amyloid-beta plaques than MS patients. Similar observations were made for the tau ratio (18.3% vs. 9%).
When the researchers performed brain scans on 11 MS patients, they found that the blood test results generally matched the brain imaging findings, especially for the APS2 and tau ratio. This means the PrecivityAD2 test is reliable for predicting amyloid-beta plaques in the brain.
The findings suggest that MS may protect against Alzheimer’s.
Moreover, MS patients positive for either APS2 or tau ratio were significantly more likely, by up to 23 times, to have two or more atypical MS features at diagnosis, suggesting that a more typical MS profile was even more protective against Alzheimer’s.
The researchers also studied the effects of a gene called APOE, which is linked to Alzheimer’s.
They found that patients carrying one or two copies of APOE3, the most common genetic APOE variant that is linked to an average risk of Alzheimer’s, had lower APS2 and tau ratio than those without MS. This protective effect wasn’t seen in MS patients with two copies of APOE4, a variant linked to a more than twofold higher risk of Alzheimer’s.
The results suggest “that MS is associated with a low prevalence of [amyloid-related damage] based on [blood] biomarkers,” the researchers wrote.
“If we could identify what aspect is protective and apply it in a controlled way, that could inform therapeutic strategies for Alzheimer’s disease,” Brier said.