The discovery suggests a new direction for Alzheimer’s treatments, said Matthew Brier, MD PhD, assistant professor of neurology and radiology and the study’s lead author.

“Our findings imply that some aspect of the biology of multiple sclerosis, or the genetics of MS patients, is protective against Alzheimer’s disease,” Brier said. “If we could identify which aspect is protective and target it in a controlled manner, that could inform therapeutic strategies for Alzheimer’s disease.”

The study, an example of clinical observations directly impacting research, was published in the Annals of Neurology.

The research, a collaboration between WashU Medicine experts in Alzheimer’s and MS, was prompted by a hunch that Brier’s mentor and collaborator, Anne Cross, MD, had developed over decades of treating patients with MS, an immune-mediated disease that affects the central nervous system. Even though her patients lived long enough to be at risk for Alzheimer’s or had a family history of the neurodegenerative disease, they did not develop the disease.

“I noticed that I couldn’t find a single MS patient of mine who had typical Alzheimer’s,” said Cross, the Manny and Rosalyn Rosenthal and Dr. John Trotter MS Center Chair in Neuroimmunology. “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 say, ‘No, this is not Alzheimer’s.’”

Cognitive impairment caused by MS can be confused with symptoms of Alzheimer’s disease. Alzheimer’s can be diagnosed with blood tests and other biological tests.

To confirm Cross’s observation, the research team used a new, FDA-approved blood test developed by researchers at WashU Medicine. The blood test, known as PrecivityAD2, is highly effective at predicting the presence of amyloid plaques in the brain. Such plaques are an indicator of Alzheimer’s disease and previously could only be verified with brain scans or spinal taps.

Brier, Cross and their colleagues recruited 100 patients with MS to take the blood test, 11 of whom also underwent PET scans at the Mallinckrodt Institute of Radiology at WashU Medicine. Their results were compared with those from a control group of 300 people who did not have MS but were similar to those with MS in terms of age, genetic risk for Alzheimer’s and cognitive decline.

“We found that 50 percent fewer MS patients had amyloid pathology compared to their matched peers, based on this blood test,” Brier said. This finding supported Cross’ observation that Alzheimer’s seemed less likely to develop in people with MS. It’s not clear how amyloid accumulation relates to the cognitive impairment characteristic of Alzheimer’s, but plaque accumulation is generally considered the first event in the biological cascade that leads to cognitive decline.

The researchers also found that the more typical the patient’s MS history, in terms of age of onset, severity and overall disease progression, the less likely they were to have amyloid plaque accumulation in their brains compared with patients with atypical presentations of MS. This suggests that there is something in the nature of MS itself that protects against Alzheimer’s, which Brier and Cross plan to investigate.

MS patients typically have multiple flare-ups of the disease over the course of their lives. During these flare-ups, the immune system attacks the central nervous system, including the brain. It is possible that this immune activity also reduces amyloid plaques, the researchers said.

“Perhaps the patients with MS, as the amyloid pathology of Alzheimer’s disease developed, had some degree of inflammation in their brains that was being fueled by their immune responses,” Brier said. Citing work by co-author David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor of Neurology, Brier noted that activated microglia, which are part of the brain’s immune response in MS, cleared amyloid from the brain in animal models.

Brier and Cross have begun the next steps in this research. They want to not only map the possible human genetics, but also test the development of amyloid plaques in animal models that mirror MS.

Several of Brier and Cross’ co-authors on the study are affiliated with C2N Diagnostics, a WashU Medicine startup that provided support for the research. The PrecivityAD2 test is based on technology licensed to C2N by the university.