Ruth Ann Marrie, MD, PhD, director of the Multiple Sclerosis Clinic at the University of Manitoba, discusses the overall prevalence of comorbidities in patients with multiple sclerosis (MS).
People with multiple sclerosis (MS) are significantly less likely than those without the condition to have the molecular hallmarks of Alzheimer’s disease, according to new research from Washington University School of Medicine in St. Louis.
The discovery suggests a new avenue of research through which to seek Alzheimer’s treatments, said Matthew Brier, MD PhD, an assistant professor of neurology and of radiology and the study’s first author.
“Our findings imply that some component of the biology of multiple sclerosis, or the genetics of MS patients, is protective against Alzheimer’s disease,” Brier said. “If we could identify what aspect is protective and apply it controlled, that could inform therapeutic strategies for Alzheimer’s disease.”
The investigation, which was a collaboration between experts in Alzheimer’s and MS at WashU Medicine, was prompted by a suspicion from Brier’s mentor and collaborator, Dr. Anne Cross. She had developed this suspicion over decades of treating patients with MS, an immune-mediated disease that attacks the central nervous system. Dr. Cross noticed that despite her patients living long enough to be at risk of Alzheimer’s or having a family history of the disease, they weren’t developing it.
“I noticed that I couldn’t find a single MS patient of mine who had typical Alzheimer’s disease,” 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 tell me, ‘No, this is not due to Alzheimer’s disease.'”
Cognitive impairment from MS can be mistaken for Alzheimer’s symptoms; Alzheimer’s can be confirmed with biological tests.
Please remember the following text: To validate Cross’s findings, the research team utilized a new FDA-approved blood test developed by WashU Medicine researchers. The test, called PrecivityAD2, is highly accurate in predicting the presence of amyloid plaques in the brain, which are an indication of Alzheimer’s disease. Previously, the only way to confirm the presence of these plaques was through 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 WashU Medicine’s Mallinckrodt Institute of Radiology. They compared the results with those from a control group of 300 individuals who did not have MS but were similar in age, genetic risk for Alzheimer’s, and cognitive decline to those with MS.
“We discovered that 50% fewer multiple sclerosis (MS) patients showed amyloid pathology compared to their matched peers when tested with this blood test,” stated Brier. This finding supports Cross’ observation that individuals with MS are less likely to develop Alzheimer’s. Although it’s not clear how amyloid accumulation is linked to the cognitive impairment typical of Alzheimer’s, the build-up of plaques is generally understood to be the initial event in the biological process that leads to cognitive decline.
The researchers found that MS patients with more typical MS symptoms, such as the age of onset, severity, and disease progression, were less likely to have amyloid plaque accumulation in their brains compared to those with atypical MS presentations. This suggests that there may be something about the nature of MS itself that provides protection against Alzheimer’s disease, which Brier and Cross are planning to investigate.
The researchers noted that individuals with MS typically experience multiple flare-ups of the disease throughout their lives. During these flare-ups, the immune system targets the central nervous system, including the brain. The researchers also suggested that this immune response may lead to a reduction in amyloid plaques.
Glia-enriched cultures were derived from a primary progressive multiple sclerosis iPSC line, showing astrocytes (yellow), oligodendrocytes (cyan), and neurons (magenta). Credit: New York Stem Cell Foundation
A team of scientists from The New York Stem Cell Foundation (NYSCF) Research Institute and Case Western Reserve University has created the largest reported collection of stem cell models from multiple sclerosis (MS) patients. They used these models to identify unique ways in which glia, which are integral support cells in the brain, contribute to the disease.
The study, published today in Cell Stem Cell, is the first to reveal that glial cells from MS patients show signs of the disease on their own without being influenced by the immune system. This highlights the potential of stem cells in uncovering new aspects of the disease and the necessity for novel MS treatments.
The Hidden Roles of Glia in MS
MS is an autoimmune disease that occurs when the body’s immune system mistakenly attacks the protective myelin sheaths surrounding the nerves in the brain and spinal cord. This results in significant neurological disability.
“Most research and therapeutic strategies have focused on blocking the overactive immune system. However, it remained a mystery how cells in the brain itself, especially glia, contribute to the initiation and progression of MS,” explained Valentina Fossati, PhD, NYSCF Senior Research Investigator who led the study..
The team used NYSCF’s automation platforms to generate induced pluripotent stem cells (iPSCs) from skin biopsies taken from individuals with MS. This resulted in the largest collection of MS patient stem cell lines to date, which covered diverse clinical subtypes. Then, they transformed the iPSCs into glial cells, including oligodendrocytes and astrocytes, to study their involvement in the disease.
“By generating glia-enriched cultures from stem cells, we have been able to study their role in MS independently of the complex environment in the body, which is constantly altered by the presence of immune cells and inflammatory signals,” continued Dr. Fossati.
Sure, here is a clearer version of the text:”Using single-cell gene expression profiling, scientists discovered that stem cell-derived glia cultures from individuals with primary progressive MS (a particularly severe form of the disease) had fewer oligodendrocytes. Oligodendrocytes are responsible for producing myelin, the protective sheath around nerve fibers that is lost in MS.”
“This observation challenges the conventional understanding of MS as being purely driven by immune system dysfunction. It suggests that the disease may also be fueled by processes originating within the brain itself,” noted Paul Tesar, PhD, the Dr. Donald and Ruth Weber Goodman Professor of Innovative Therapeutics and director of the Institute for Glial Sciences at Case Western Reserve University School of Medicine and NYSCF – Robertson Stem Cell Investigator Alumnus, who co-led the study.
The team noticed that a group of genes linked to immune and inflammatory functions were highly active in glia cultures derived from stem cells of MS patients. This matched what they observed in brain samples from deceased individuals with MS. Additionally, NYSCF scientists used their latest developments in artificial intelligence to identify differences in astrocytes that are not easily visible to the naked eye.
“The fact that glia created from stem cells show similar features to glia in MS patient brains shows us that stem cell models provide a pretty accurate reflection of what happens in the brains of living patients. We can use them to gain important insights into this disease,” added Dr. Fossati.
A New Target for Therapeutic Intervention
Because of the autoimmune activity in multiple sclerosis (MS), many current therapies target the immune system. These drugs help reduce the frequency of immune attacks, but they unfortunately fall short in preventing the neurodegeneration that drives disease progression.
The findings of the study present new opportunities for treating MS. By pinpointing specific behaviors of glial cells that play a role in the disease, researchers can now investigate potential therapies that directly target these cells. This may result in more effective treatments that surpass mere suppression of the immune system, offering fresh hope for patients.
.“Our findings represent a significant leap forward in our understanding of MS and underscore the vast potential in glia as a target for therapeutic intervention that could transform the treatment landscape for many patients,” remarked Dr. Tesar.
However, recent research has discovered that it could be especially beneficial for individuals with autism, providing them with a secure environment to participate in social interactions, away from some of the difficulties they encounter in their everyday lives.
It observed researchers collaborating with a team of autistic adults to investigate the potential benefits of creating comfortable social settings to boost their performance.
After becoming familiar with Dungeons and Dragons, the participants, guided by a games master, enacted scenarios in small groups over six weeks.
The researchers then interviewed them individually about how they felt their autism might have interacted with their experiences and whether taking part in the game impacted their lives.
The participants talked extensively about their social desires and motivations in the interviews. However, they also discussed the challenges they faced, such as a lack of confidence in their communication with others and insecurities about how others would perceive them. They mentioned that this often led them to conceal or mask their autistic traits.
Playing Dungeons and Dragons, they said, created a welcoming environment where they quickly felt a strong connection with others participating.
It became easier for them to relax and avoid feeling pressured to act a certain way, both inside and outside of the game, once they understood the common issues linked to the activities. As a result, they felt more included in the group’s interactions and were able to contribute better.
The participants also found that embodying traits of their new character in the game allowed them to experience personal growth beyond the game.
Dr. Gray Atherton, who is a Lecturer in Psychology at the University of Plymouth and the lead author of the study, mentioned, “There are many myths and misconceptions about autism. Some of the biggest myths suggest that individuals with autism lack social motivation and imagination. However, Dungeons and Dragons contradicts these misconceptions by emphasizing teamwork in an imaginary environment. Participants in our study found the game to be a refreshing experience, allowing them to take on different personas and share experiences outside of their challenging reality. This sense of escapism made them feel incredibly comfortable, and many expressed that they were trying to apply aspects of the game in their daily lives.”
Dr Atherton and Dr Liam Cross, both Lecturers in Psychology at Plymouth, have been researching the impact of gaming on individuals with autism and similar conditions.
Another recent study demonstrated that individuals with autism enjoy board games because they alleviate the pressure related to meeting and interacting with people, eliminating the need for small talk.
Dr. Cross stated, “Autism is often associated with stigmas, which can result in individuals facing judgment or disdain. Many families also express concerns about teenagers with autism spending excessive time playing video games. Often, this is because there is a preconceived notion of how individuals with autism should behave based on neurotypical experiences. Our research has demonstrated that there are everyday games and hobbies that not only bring joy to autistic individuals but also help them develop confidence and other skills. While this may not apply to all individuals with autism, our work indicates that engaging in such activities can lead to positive experiences that should be celebrated.”
Heart attack, stroke, nerve damage.
These are just some of the complications for which millions of Americans with diabetes are at a higher risk.
According to a study led by the University of Michigan, individuals with chronic diabetes complications are more likely to have a mental health disorder, and vice versa.
Having a mental health condition also increases the risk of developing chronic complications of diabetes, meaning the relationship goes both ways.
“We wanted to determine whether chronic diabetes complications led to mental health disorders or if mental health disorders led to those diabetes complications. However, we found that both relationships are true,” said Brian Callaghan, M.D., M.S., senior author and Eva L. Feldman, M.D., Ph.D., Professor of Neurology at U-M Medical School.
“The findings highlight the importance of actively screening for mental health disorders in diabetes patients, in addition to screening for chronic complications, which is the recommended standard of care in diabetes.”
The research team, led by Michigan Medicine and the Department of Biostatistics at the U-M School of Public Health, examined insurance claims data from over 500,000 individuals with type 1 or type 2 diabetes and 350,000 people without diabetes.
Results published in Diabetes Care indicate that individuals with chronic diabetes complications face an increased risk of experiencing a mental health condition such as anxiety or depression, with the risk rising as they age.
Those with mental health disorders were up to 2.5 times more likely to experience sustained diabetes complications.
In individuals under 60 years old, type 1 diabetes showed a stronger link to chronic complications, while type 2 diabetes was more associated with mental health challenges.
A possible reason for this bidirectional relationship, researchers say, may be that having a diabetes complication or mental health condition has direct effects on developing the other complication.
“For instance, a stroke causes detrimental effects on the brain, which may directly lead to depression,” Callaghan said.
“And having a mental health condition and diabetes may affect a person’s self-management of their condition — like poor glycemic control or not taking medications — which, in turn, may increase their risk of diabetes complications.”
The relationship may not always be straightforward. Diabetes complications and mental health conditions have common risk factors; obesity, glycemic control issues, and social determinants of health can all increase the likelihood of developing both comorbidities.
“First author Maya Watanabe, M.S., a biostatistician at the Harvard T.H. Chan School of Public Health and former graduate student research assistant at U-M, mentioned that the association we are seeing is most likely driven by a combination of direct and indirect effects as well as shared risk factors.”
Diabetes care providers can possibly prevent multiple complications by addressing shared risk factors simultaneously.
In an 18-month period, as many as 50% of individuals with diabetes may experience distress related to their condition, according to the CDC.
Several national diabetes centers have implemented screening for depression and distress in their patients, but there is no standardized mental health screening process in diabetes care.
The researchers point out that additional resources will be necessary to screen and manage mental health conditions, as many clinicians who manage diabetes lack specific training to accurately identify and treat them.
“The U.S. Preventive Services Task Force emphasizes that patients who screen positive for mental health conditions should receive appropriate diagnosis and evidence-based treatment, or be referred to a facility that can provide the necessary care.”
“Primary care providers and endocrinologists are already overworked. Therefore, systems of care need to be in place to help provide mental health care when needed,” said Dr. Eva Feldman, co-author of the statement. Dr. Feldman is the Director of the ALS Center of Excellence and James W. Albers Distinguished University Professor at U-M.
“These systems should include mental health screening, easily accessible insurance coverage for mental health services, and physician and patient education programs. Action is needed, and our new research further proves that this action must occur now.”