ROCHESTER, Minn. — Mayo Clinic researchers have developed a new method to identify which proteins are most likely to trigger an immune response — a discovery that could help improve transplant care, regenerative biotherapeutics and other areas of medicine where the immune system plays a critical role.

The results, published in Biomaterials, challenge a common assumption in the field that all proteins are equally likely to provoke immune reactions.

"Some proteins can trigger a very strong response even when only tiny amounts remain, while others are much less troublesome," says Leigh Griffiths, Ph.D., MRCVS, senior author of the study and a researcher at Mayo Clinic. "That gives us a much clearer roadmap for designing safer, more durable biomaterials."

The team's approach combines two factors: how much of each protein is present and how strongly it activates the immune system. By integrating these measurements, researchers can rank proteins from the most immunogenic to the least, revealing which ones matter most.

The researchers call this measurement the Ratio of Immunogenicity, or ROI. Applying it across hundreds of proteins revealed patterns that had not been clearly recognized before.

One of the most striking findings involved mitochondria — structures inside cells best known for producing energy. The study found that mitochondrial proteins were far more likely to evoke strong immune responses than proteins from other parts of the cell, accounting for more than a quarter of the most immunogenic proteins identified. Mitochondria likely evolved from ancient bacteria, and that evolutionary history may help explain why the immune system appears especially sensitive to them when they are exposed.

"We think the body has never fully accepted mitochondria as part of itself — they're normally hidden inside the cell, and when they're exposed, the immune system may still recognize them as foreign," says Dr. Griffiths.

The implications extend beyond tissue engineering. The researchers say the same strategy could help identify the most important immune targets in organ transplantation, infectious diseases and cancer biology. In transplantation, for example, ranking the most immunogenic proteins could eventually help scientists develop better biomarkers to detect rejection earlier or guide more targeted therapies.

The work also aligns with Mayo Clinic's Genesis strategic initiative by advancing the science needed to create next-generation regenerative medicine products. Dr. Griffiths' laboratory is already using these insights to refine engineered tissues intended for clinical use, with the goal of removing the proteins most likely to cause harmful immune reactions while preserving the structure needed for healing and integration.

"This study fills a critical gap in knowledge," Dr. Griffiths says. "If we want to build regenerative therapies and implants that are truly safe and effective, we need to understand not just that the immune system is reacting, but what exactly it is reacting to. That understanding is what will help move better products to patients."

For a complete list of authors, disclosures and funding, review the study. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:

• Terri Malloy, Mayo Clinic Communications, newsbureau@mayo.edu

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On a global stage in Berlin, surrounded by leading scientists and engineers in quantum computing, a Mayo Clinic team earned first place at the Berlin Quantum Hackathon 2026.

The five-week hackathon challenged six finalist teams to prove that quantum computing — one of science's newest and most complex frontiers — can solve meaningful problems beyond theory. More than 180 teams applied to compete. The awards were presented on March 5.

The Mayo team built a novel quantum-powered model capable of detecting movement intention directly from brain activity. 

Code, circuits and possibility

Inside the competition hall, conversations unfolded in the language of quantum science — qubits, circuits and optimization algorithms. Teams presented performance metrics to an expert judging panel that challenged assumptions and tested claims on the spot. Technical execution, scalability and real-world impact all factored into the score.

Among them stood a Mayo Clinic team that had begun studying quantum computing only a year earlier.

They approached the challenge the way Mayo Clinic approaches medicine: with the patient at the center and the science pushed to its limits.

Decoding the intent to move

The team's work began with a clinical question: What happens when the brain intends to move, but the body cannot?

In people living with paralysis or other motor impairments, the brain still sends the signal, carrying intention across neural networks even when the body cannot respond.

The team set out to detect that signal by distinguishing the intent to move a left hand from a right — a subtle difference buried within the brain's constant electrical rhythm.

They drew on electroencephalogram, or EEG, recordings, which capture the brain's electrical activity as continuous waves layered with motion and background noise.

To isolate that distinction, they built a hybrid system that combined advanced AI with emerging quantum tools. That required learning the language of quantum science.

"One of our secrets to success was focusing on the complete solution, not just the computational challenge," says Dr. Rickey Carter, professor of biostatistics at Mayo Clinic and the team leader. "We built around patients' needs and paid close attention to the edge cases where the model struggled. That's where we concentrated our quantum efforts."

If validated in future research, such signals could one day help guide assistive technologies or prosthetics, potentially enabling more precise control of movement.

At the leading edge of discovery 

For Dr. Charles Bruce, chief innovation officer at Mayo Clinic in Florida, the hackathon reflected a broader commitment: building bridges across disciplines and borders in a field that advances through shared expertise.

"Standing alongside leaders in this field strengthened our work and reminded us that advancement happens together," Dr. Bruce says. "We entered this challenge as underdogs. None of us had prior quantum computing experience. But progress is built collectively. You learn from one another, blending biology with data science, and the work becomes stronger because of it."

The multidisciplinary team from Mayo Clinic in Florida — Dr. Carter, Miko Wieczorek, Dr. Michele Dougherty, Dr. Feifei Li and Dr. Bruce — built the model from the ground up. Mayo Clinic's Quantum Sensing and Computing program supported the effort, exploring how emerging quantum technologies may intersect with patient care.

Miko Wieczorek, a data scientist in the Mayo Clinic Digital Innovation Lab, led the team's work running the model on a quantum computer — a first for Mayo.

"When our model executed successfully on a quantum computer, it felt like stepping into the next chapter of science," Wieczorek says. "In that moment, we realized we weren't just observing this field — we were helping shape it."

Dr. Michele Dougherty, a medical physicist in Radiation Oncology, contributed expertise in complex optimization.

"Quantum computing could eventually help us design safer and more precise radiation treatments," she says. "If it accelerates how we find the best possible plan for a patient, that's meaningful."

Dr. Feifei Li, a former theoretical physicist who is now a medical physicist in Radiation Oncology at Mayo Clinic, says the project highlights how quantum computing could expand the boundaries of medical research.

"Some scientific questions remain unsolved not because we lack data, but because of how difficult they are to model," Dr. Li says. "Quantum computing gives us a different way to approach that complexity."

Quantum computing moves toward application

The event was hosted by Berlin-based quantum software company Kipu Quantum and supported by the State of Berlin's Quantum Initiative and the Charité-Berlin University Medicine.

"Quantum computing is proving this year that we can design hybrid quantum-classical solutions for tackling industrial problems," says Enrique Solano, CEO of Kipu Quantum. "Medical imaging and life science will occupy a key role in the list of applications. By winning the hackathon, Mayo Clinic is making an important step toward this visionary goal."

Shaping the frontier 

For the Mayo Clinic team, the Berlin hackathon reaffirmed that real progress begins with curiosity, collaboration and the courage to explore uncharted territory. Together, they showed how multidisciplinary teams can carry some of healthcare's most pressing challenges toward its next frontier.

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ROCHESTER, Minn. — Alzheimer's-related brain changes progressed up to 20 times faster in women who also had abnormal levels of a Parkinson's-related protein, according to a Mayo Clinic study published in JAMA Network Open. The same pattern was not observed in men.

The findings suggest that when alpha-synuclein — a protein linked to Parkinson's disease — accumulates alongside Alzheimer's pathology, it may drive faster disease progression in women. That interaction could help explain a long-standing disparity: women make up nearly two-thirds of people living with Alzheimer's disease in the U.S.

Kejal Kantarci, M.D., a Mayo Clinic neuroradiologist and senior author of the study, uses advanced brain imaging to track Alzheimer's progression.

"Recognizing these sex-specific differences could help us design more targeted clinical trials and ultimately more personalized treatment strategies," Dr. Kantarci says. "When we see disease-related changes unfolding at dramatically different rates, we cannot keep approaching Alzheimer's as though it behaves exactly the same way in everyone. Co-pathologies may impact the disease process."

Alzheimer's disease is marked by the buildup of tau protein in the brain. Many people along the Alzheimer's disease continuum also develop abnormal clumping of α-synuclein, a protein associated with Lewy body diseases such as Parkinson's disease and dementia with Lewy bodies.

Tau and α-synuclein occur naturally in the brain. In neurodegenerative diseases, however, these proteins can misfold and clump together, forming abnormal deposits. This pathological buildup disrupts communication between brain cells and contributes to cognitive decline.

Researchers set out to determine whether having both abnormal protein buildups alters how the disease progresses and whether that effect differs between women and men.

To investigate, the team analyzed data from 415 participants in the Alzheimer's Disease Neuroimaging Initiative, a national research consortium that tracks brain changes over time. Participants underwent cerebrospinal fluid testing to detect abnormal α-synuclein and repeated brain imaging to measure changes in tau accumulation. About 17% of participants showed evidence of abnormal α-synuclein.

Among participants with both Alzheimer's-related pathology and α-synuclein abnormalities, women accumulated tau dramatically faster than men with the same coexisting protein changes.

Elijah Mak, Ph.D., first author of the study and a Mayo Clinic neuroimaging researcher, studies how multiple brain pathologies interact and drive disease progression.

"This opens an entirely new direction for understanding why women bear a disproportionate burden of dementia," Dr. Mak says. "If we can unravel the mechanisms behind this vulnerability, we may uncover targets we haven't considered before."

The researchers are now examining whether these sex-specific effects also appear in patients with dementia with Lewy bodies, where α-synuclein is the primary disease driver rather than a coexisting pathology. The work will help determine whether the observed difference is unique to Alzheimer's disease or reflects a broader sex-specific vulnerability across neurodegenerative conditions.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

 Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers link Parkinson’s-related protein to faster Alzheimer’s progression in women  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have identified a hidden "movement map" deep within the brain — a discovery that could help surgeons reduce side effects from epilepsy procedures and guide future treatments for speech and movement disorders.

In a study published Feb. 18 in the Proceedings of the National Academy of Sciences, the team reports that a small, buried brain region called the insula contains its own organized map of the body. Distinct areas within the insula are linked to movement of the hands, feet, and tongue.

The finding has immediate relevance for epilepsy care. Surgeons sometimes operate in or near the insula to treat seizures, and up to 30% of patients can experience temporary problems with speech, swallowing or hand movement afterward. Until now, doctors did not have detailed maps showing exactly where those functions are located in this deep brain region.

"If we can identify where hand and speech functions live in each patient, we can better anticipate — and potentially avoid — those deficits," says Panos Kerezoudis, M.D., a Mayo Clinic neurosurgery resident and lead author of the study. "This gives us a practical roadmap."

The insula sits several centimeters beneath the brain's surface, hidden under other lobes, which has made it difficult to study with traditional techniques.

"For a long time, people thought this region was generally active during many tasks — more of an integrator than a structured map," says Dr. Kerezoudis. "We wanted to know whether it follows the same organized layout we see in the main motor cortex, or if it responds the same way no matter what you move."

To answer that question, researchers in the Cybernetics and Motor Physiology Lab at Mayo studied 18 patients with medically refractory epilepsy who had thin recording electrodes placed deep in their brains as part of their clinical care.

While hospitalized, patients performed simple movements such as opening and closing their hand, moving their tongue, or flexing their foot. The electrodes recorded electrical activity in both the insula and the primary motor cortex, the brain's main movement center, with millisecond precision.

The results showed clear organization: hand movements activated one area of the insula, tongue movements another and foot movements yet another, though less prominently.

"We found distinct body-part representation in this deep structure," says Dr. Kerezoudis. "It is not random. There is order."

The timing of activity was also revealing. The primary motor cortex became active first, followed by the insula, and then movement occurred.

"This shows that the insula is not simply reacting after we move," says Kai Miller, M.D., Ph.D., a Mayo Clinic neurosurgeon and senior author of the study. "This discovery expands our understanding of how movement is supported by a distributed brain network whose parts are more tightly integrated than we previously thought. By mapping it carefully, we can make brain surgery and neuromodulation safer, more precise, and beneficial for more people."

In a subset of patients, researchers delivered brief, safe electrical pulses to test how the regions communicate. Stimulating a hand-related area in the motor cortex triggered a response in the matching area of the insula, and the same pattern held for tongue regions.

"The connections respect the body map — hand connects to hand, tongue to tongue," says Dr. Kerezoudis. "That strengthens the case that this is an organized network."

Clinically, the findings could help neurologists better interpret seizure symptoms, such as hand contractions or facial movements, and refine electrode placement during epilepsy evaluations. Surgeons may also use individualized maps to plan procedures more precisely.

Beyond epilepsy, the work may inform future therapies for stroke survivors with speech or hand movement difficulties. If movement relies on a network that includes both the primary motor cortex and the insula, treatments such as targeted brain stimulation may need to address both areas.

The study supports Mayo Clinic's Bioelectronic Neuromodulation Innovation to Cure (BIONIC) initiative by using advanced brain-recording technology to translate scientific discoveries into practical care strategies. It also aligns with Pre-cure, which focuses on anticipating and preventing complications before they occur — such as identifying critical movement areas before surgery rather than reacting to deficits afterward.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers discover hidden brain map that may improve epilepsy care appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — The brain may inadvertently "learn" to have seizures by treating them like important memories to be stored, according to new research from Mayo Clinic.

The study, published in the Journal of Neuroscience, found that after a seizure, the brain enters a deep sleep state that mimics memory storage — and that this effect can persist into the following night's sleep. In effect, this "saves" the seizure's path like a normal memory, strengthening the disease. The findings suggest new opportunities to prevent epilepsy from worsening by targeting brain activity during the hours immediately following a seizure and during the subsequent night of sleep — a critical period when harmful brain changes may occur.

"Sleep is one of the brain's most powerful tools for learning and memory," says Vaclav Kremen, Ph.D., a neuroscientist and engineer at Mayo Clinic and lead author of the study. "What we're seeing is that after a seizure, the brain may be engaging the same biological processes used to consolidate memories, but instead reinforcing the networks that generate seizures."

Epilepsy affects an estimated 50 million people worldwide, and many patients continue to have seizures despite medication. Understanding the relationship between seizures and sleep could help explain why epilepsy can worsen over time and why memory, mood and sleep problems are common in people with the condition.

The study analyzed long-term brain recordings from implanted devices in 11 people with epilepsy. Using these recordings, researchers compared sleep patterns on nights following seizures to nights when no recent seizures occurred.

They found that after a seizure, the brain consistently entered a prolonged and intensified state of deep sleep, known as non-rapid eye movement (NREM) sleep. During this period, slow brain waves became stronger and steeper — key features of memory consolidation — particularly within the specific brain regions where seizures originate.

At the same time, rapid eye movement (REM) sleep, which is important for emotional processing and cognitive health, was reduced. On average, patients slept longer and spent more time in deep sleep after seizures, but they experienced less REM sleep compared with seizure-free nights.

The researchers call this process seizure-related consolidation, a phenomenon in which seizures appear to hijack the brain's normal learning mechanisms. Rather than helping the brain recover, this post-seizure sleep state may strengthen abnormal neural circuits, creating a vicious cycle in which each seizure increases the likelihood of future seizures.

"Instead of treating seizures as isolated events, this research shows they may actively shape the brain in ways that promote disease progression," says Dr. Kremen.

Importantly, the findings point to a potential new window for treatment — the hours and nights after a seizure — when targeted intervention could disrupt this harmful learning process.

"If we can safely intervene during this post-seizure window, we may be able to weaken seizure networks rather than reinforce them,” says Gregory Worrell, M.D., Ph.D., a neurologist at Mayo Clinic and senior author of the study.

These insights support Mayo Clinic's Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative, which aims to devise personalized neuromodulation therapies to prevent, treat, and potentially reverse neurological disease. By combining long-term brain sensing, advanced analytics and an understanding of how the brain adapts after seizures, the study highlights the potential for bioelectronic approaches to promote healthier brain function.

Future research will focus on translating these discoveries into BIONIC-enabled therapies, including adaptive closed-loop brain stimulation systems designed to respond to seizures and sleep states in real time. Mayo Clinic researchers have already begun designing next-generation approaches aimed at breaking this cycle and restoring normal brain activity.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Brain may reinforce seizures during sleep, Mayo Clinic study suggests appeared first on Mayo Clinic News Network.

These discoveries reflect progress across three major innovation efforts at Mayo Clinic. Mayo Clinic clinicians and scientists are working together to develop tools to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions through the Precure initiative. They are advancing new cures for end-organ failure beyond traditional transplantation as part of the Genesis initiative. They are also uniting clinical insight with cutting-edge engineering to deliver novel neurological diagnostics and therapies through the Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative. 
 

1. 'Virtual clinical trials' may predict success of heart failure drugs 

Mayo Clinic researchers have created "virtual clinical trials" that advance the discovery of therapies while reducing time, cost and the risk of failed studies by combining advanced computer modeling with real-world patient data as part of the Precure and Genesis initiatives. Through one virtual clinical trial, they have developed a new way to predict whether existing drugs could be repurposed to treat heart failure, one of the world's most pressing health challenges. 

"Clinical trials will always remain essential," says Cui Tao, Ph.D., the Nancy Peretsman and Robert Scully Chair of Artificial Intelligence and Informatics and vice president of Mayo Clinic Platform Informatics. "But this innovation demonstrates how AI can make research more efficient, affordable and broadly accessible. Integrating trial emulation, simulation, synthetic trials and biomedical knowledge modeling opens the door to a new paradigm in translational science." 

2. New discovery may unlock regenerative therapies for lung disease

Mayo Clinic researchers have uncovered the molecular "switch" that directs a small but powerful set of cells that choose whether to repair tissue or fight infection, a discovery that could inform regenerative therapies for chronic lung diseases, which is part of Mayo Clinic's Genesis initiative.
 
"We were surprised to find that these specialized cells cannot do both jobs at once," says Douglas Brownfield, Ph.D., senior author of the study. "Some commit to rebuilding, while others focus on defense. That division of labor is essential — and by uncovering the switch that controls it, we can start thinking about how to restore balance when it breaks down in disease." 

3. Stem cells may offer new hope for end-stage kidney disease treatment

Mayo Clinic researchers found that injecting patients' own stem cells from fat cells into the vein before hemodialysis, a treatment for end-stage kidney disease, often helped prevent inflammation and vein narrowing. This could help millions of people tolerate dialysis longer, extending the time before they require a kidney transplant as part of the Mayo Clinic Genesis initiative. 

"This approach has the potential to improve outcomes for millions of patients with kidney failure, reduce healthcare costs and inform new clinical guidelines for dialysis access management if validated in larger clinical trials," says Sanjay Misra, M.D., a Mayo Clinic interventional radiologist. 

4. Mayo Clinic physicians map patients' brain waves to personalize epilepsy treatment

Using detailed maps of each patient's unique brain wave patterns, Mayo Clinic physicians can now pinpoint where stimulation is most effective, moving beyond the traditional one-size-fits-all approach to epilepsy treatment. This research is part of the BIONIC initiative.

"The long-term goal is to quiet the seizure network, so it is eventually forgotten. Reorganizing the neuronal network could move us beyond controlling seizures to actually curing epilepsy," says Nick Gregg, M.D., a Mayo Clinic neurologist. 

5. New genetic biomarker flags aggressive brain tumors

Mayo Clinic researchers found when meningiomas — the most common type of brain tumor — show activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low grade under the microscope. This is part of the Mayo Clinic Precure initiative. 

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

6. Mayo Clinic researchers discover the immune system's 'fountain of youth'

Mayo Clinic researchers have found that some older people maintain "immune youth" – a new term coined by Mayo researchers to explain a young immune system in someone over age 60.  
 
"We observed that these patients have very young immune systems despite being in their 60s and 70s. But the price they pay for that is autoimmunity," says Cornelia Weyand, M.D., Ph.D., a Mayo Clinic rheumatologist and clinician-scientist. This is part of the Mayo Clinic Precure initiative.

7. Mayo Clinic tools predict, identify and diagnose Alzheimer's, dementia quicker

Mayo Clinic researchers have developed new tools to estimate a person's risk of developing Alzheimer's disease years before symptoms appear as part of the Precure initiative and to help clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using one scan. They also confirmed the accuracy of an FDA-approved blood test that can be used at outpatient memory clinics to diagnose the disease in patients with a range of cognitive impairment. 

"Every patient who walks into my clinic carries a unique story shaped by the brain's complexity," says David T. Jones, M.D., a Mayo Clinic neurologist. "That complexity drew me to neurology and continues to drive my commitment to clearer answers."

8. Mayo Clinic research improves dense breast cancer screening and early detection

Nearly half of all women in the U.S. have dense breast tissue, which can make detecting breast cancer difficult with a mammogram. Mayo Clinic researchers found that adding another test, called molecular breast imaging, or MBI, to a 3D mammogram, improved the ability to find cancer in dense tissue by more than double. 
 
"Our research focuses on detecting the most lethal cancers, which can include invasive tumors that grow quickly. If these are detected earlier, we likely can save more lives," says Carrie Hruska, Ph.D., a Mayo Clinic professor of medical physics and lead author of the study. 

9. Mayo Clinic researchers find 'sugar coating' cells can protect those typically destroyed in type 1 diabetes

After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, Mayo Clinic researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes. 

"A goal would be to provide transplantable cells without the need for immunosuppression," says Virginia Shapiro, Ph.D., a Mayo Clinic immunology researcher. "Though we're still in the early stages, this study may be one step toward improving care."

10. New study calculates autoimmune disease prevalence

Mayo Clinic researchers and collaborators have described — for the first time — the prevalence of autoimmune diseases in the U.S. Their research reports that about 15 million people are estimated to have one or more of 105 autoimmune diseases. The study also found that autoimmune diseases occur most often in women, and it identified the top autoimmune diseases by prevalence, sex and age. 
 
"Knowing the number of patients with an autoimmune disease in the U.S. is critical to assess whether these diseases are increasing or decreasing over time and with treatment," says DeLisa Fairweather, Ph.D., vice-chair of translational research for the Department of Cardiovascular Medicine at Mayo Clinic in Florida and corresponding author of the study.

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact: 

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post A Year of Discovery: 10 Mayo Clinic research breakthroughs moving medicine forward  appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have uncovered how aging "zombie cells" trigger harmful inflammation that accelerates a severe and increasingly common form of fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH). As obesity rates rise worldwide, MASH is projected to increase and is already one of the leading causes of liver transplantation. 

"Liver scarring and inflammation are hallmarks of MASH. If left untreated, it can progress to liver cancer. This is why it's so important to understand the mechanisms driving the disease so that we can prevent it or develop more effective treatments," says Stella Victorelli, Ph.D., who is the lead author of the study published in Nature Communications.  

Dr. Victorelli and colleagues, who study aged or senescent "zombie" cells, identified a mechanism by which these cells drive liver scarring and inflammation. They found that small molecules called mitochondrial RNA, typically found within the cell's energy-producing mitochondria, can leak into the main part of the cell, where they mistakenly activate antiviral sensors called RIG-I and MDA5 — normally triggered when a virus infects a cell. In this case, the danger signal comes from the cell's own mitochondria, prompting a wave of inflammation that can damage nearby healthy tissue. 

When the researchers blocked the sensors, inflammation dropped sharply. The study also found that proteins BAX and BAK, which help open pores in the mitochondrial membrane, enable mitochondrial RNA to escape. In a preclinical MASH model, inhibiting BAX and BAK prevented RNA from escaping and was associated with less inflammation and healthier liver tissue. 

What are 'zombie' cells?

As we age, some cells enter senescence — a state in which they stop dividing but continue releasing inflammatory and tissue‑damaging molecules. When people are young, the immune system typically eliminates these senescent, or "zombie," cells. With age, however, they can persist and contribute to a range of age‑related health problems and diseases. 

While some research focuses on removing these cells, this team investigated how to quiet their harmful signals.  

"With age, we accumulate 'zombie' cells, which can lead to more disease," says João Passos, Ph.D., senior author of the study. "Our idea is that if we can quiet these cells earlier, we can prevent runaway inflammation and the development of many age‑related conditions, including liver disease. Understanding the mechanisms that drive disease allows us to target and delay those processes — potentially benefiting more than one condition." 

Dr. Passos and colleagues also are developing new technology to spatially map senescent cells throughout the body during aging. 

This research was conducted in partnership between the Robert and Arlene Kogod Center on Aging and the Center for Cell Signaling in Gastroenterology (C-SiG) at Mayo Clinic. 

The research is part of a larger effort at Mayo Clinic called the Precure initiative, which is focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions. 

Review the study for a complete list of authors, disclosures and funding.   

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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact: 

• Kelley Luckstein, Mayo Clinic Communications, newsbureau@mayo.edu

The post ‘Zombie’ cells spark inflammation in severe fatty liver disease, Mayo Clinic researchers find  appeared first on Mayo Clinic News Network.

At Mayo Clinic, biomedical engineer Benjamin Brinkmann, Ph.D., is developing tools and technologies that help reveal brain patterns — making epileptic seizures more predictable and, one day, preventable. 

In a neurology lab at Mayo Clinic, Dr. Benjamin Brinkmann studies the brain's electrical rhythms across days, weeks and months — searching for patterns that reveal when seizures are most likely to occur. Working with neuroscientists and clinicians, he combines data from brain waves, vital signs and imaging to develop tools that interpret those signals and help guide patient care. 

Epilepsy is a brain disorder that causes recurring seizures — sudden bursts of electrical activity that can interrupt movement, speech or awareness. About 3.4 million people in the U.S. live with the condition. For many, medication keeps seizures under control. But for those with drug-resistant epilepsy, the episodes can occur without warning — disrupting routines and independence. 

Dr. Brinkmann, a biomedical engineer, has dedicated his career to improving care for people with epilepsy. Working with Mayo Clinic's epilepsy team, he helps identify where seizures begin in the brain — essential information for those whose epilepsy is difficult to control. His long-term goal is to move from forecasting seizures to stopping them before they start. 

A clearer picture of epilepsy, one signal at a time

One example of that work is a study Dr. Brinkmann led with international collaborators. They tested a small implant that sits just under the skin behind the ear, recording brain activity as people go about their day. The device helps provide a more accurate picture than seizure diaries, which can miss or misclassify episodes. Accurate and continuous monitoring helps doctors track seizure patterns and adjust treatment.

Over 15 months, the team collected more than 72,000 hours of brainwave data from people with epilepsy. They recorded 754 seizures — nearly twice as many as were reported in diaries. About half of the study participants wore the device more than 20 hours a day and reported it did not interfere with daily life. The findings suggest that long-term, at-home brain monitoring can uncover seizure patterns missed in short clinic visits. 

Smartwatch uses AI to forecast seizures 

Dr. Brinkmann also led a study on wearable technology — a smartwatch that uses artificial intelligence to help forecast seizures before they happen. 

The watch tracks heart rate, movement, skin conductance and temperature, using machine learning to help clinicians find patterns that may signal a seizure. In findings published in Epilepsia, the team correctly predicted about 75% of seizures, with few false alarms. 

Dr. Brinkmann says the idea is simple: to give people a warning. A few minutes' notice can mean calling a caregiver, sitting down or avoiding a risky activity. In the future, those alerts could even trigger treatments automatically, using medication or gentle brain stimulation when seizure risk is high. 

Building the future of epilepsy care

Together, the implant and smartwatch studies show what's possible when brain activity can be tracked continuously. The research is opening a new window into how seizures develop and helping shape the next generation of neurotechnology at Mayo Clinic. 

Dr. Brinkmann's work contributes to Mayo's BIONIC program — short for Bioelectronics Neuromodulation Innovation to Cure — which unites scientists and clinicians to develop smarter, more responsive technologies and therapeutics for the brain, spine and nervous system. The goal is ambitious: systems that can sense trouble and respond instantly to stop it. 

In Dr. Brinkmann's lab, every signal adds to that future — each one bringing a clearer picture of epilepsy and what care might look like in the years ahead. 

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ROCHESTER, Minn. — Clinicians typically classify meningiomas — the most common type of brain tumor — into three grades, ranging from slow-growing to aggressive.

But a new multi-institutional study suggests that appearances may be deceiving. If a tumor shows activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low-grade under the microscope.

The findings, published in Lancet Oncology, could significantly change how doctors diagnose and treat meningiomas.

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

This research was presented at the Society for Neuro-Oncology conference on Nov. 22.

"This is one example of how precision diagnostics of cancer may ultimately improve patient outcomes," says Kenneth Aldape, M.D., Mayo Clinic pathologist and study co-author.

An early warning sign

Meningiomas — tumors of the meninges, the protective tissue that surrounds the brain and spinal cord — are generally considered benign. But a small subset of these tumors has a mutation in the TERT gene, which is linked to faster growth and a shorter time before the tumor returns after treatment.

TERT is the active part of telomerase, an enzyme that maintains telomeres, the protective ends of chromosomes. In most healthy adult cells, TERT is switched off. But if it becomes switched back on, it can fuel cancer development by driving unchecked cell growth.

In this study, the researchers wanted to see whether high TERT expression, even in the absence of the TERT genetic mutation, also predicted worse outcomes. They looked at more than 1,200 meningiomas from patients across Canada, Germany and the U.S., and they found that nearly one-third of them had high TERT expression despite not having the mutation.

These patients had earlier tumor regrowth compared to those without TERT expression, though their outcomes were better than patients with full-blown TERT mutations.

"TERT-positive tumors behaved like they were one grade worse than their official diagnosis," says Dr. Zadeh. "For example, a grade 1 tumor with TERT expression acted more like a grade 2."

Guiding treatment decisions

The findings suggest that testing for TERT activity could help doctors predict which patients are at higher risk for recurrence and may need closer monitoring or more intensive treatment.

"Because meningiomas are the most common primary brain tumor, this biomarker could influence how thousands of patients are diagnosed and managed worldwide," says Dr. Zadeh.

"TERT expression can help us more accurately identify patients with aggressive meningiomas," Chloe Gui, M.D., a neurosurgery resident at the University of Toronto, Mayo Clinic research collaborator and the study's lead author, explains on a podcast hosted by The Lancet Oncology. "This information allows us to offer treatment tailored to the tumor's behavior."

The team is currently investigating ways to incorporate TERT expression into the clinical workflow. The research is part of a larger effort at Mayo Clinic called the Precure initiative, focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

Review the study for a complete list of authors, disclosures and funding. 

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and to providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post New genetic biomarker flags aggressive brain tumors appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — Mayo Clinic researchers have developed a new tool that can estimate a person's risk of developing memory and thinking problems associated with Alzheimer's disease years before symptoms appear. The research, published in The Lancet Neurology, builds on decades of data from the Mayo Clinic Study of Aging — one of the world's most comprehensive population-based studies of brain health.

The study found that women have a higher lifetime risk than men of developing dementia and mild cognitive impairment (MCI), a transitional stage between healthy aging and dementia that often affects quality of life but still allows people to live independently. Men and women with the common genetic variant, APOE ε4, also have higher lifetime risk.

Predicting Alzheimer's disease

Alzheimer's disease is marked by two key proteins in the brain: amyloid, which forms plaques, and tau, which forms tangles. Drugs recently approved by the Food and Drug Administration remove amyloid from the brain and can slow the rate of disease progression for people with MCI or mild dementia.

"What's exciting now is that we're looking even earlier — before symptoms begin — to see if we can predict who might be at greatest risk of developing cognitive problems in the future," says Clifford Jack, Jr., M.D., radiologist and lead author of the study.

The new prediction model combined several factors, including age, sex, genetic risk as associated with APOE genotype and brain amyloid levels detected on PET scans. Using the data, researchers can calculate an individual's likelihood of developing MCI or dementia within 10 years or over the predicted lifetime. Of all the predictors evaluated, the brain amyloid levels detected on PET scans was the predictor with the largest effect for lifetime risk of both MCI and dementia.

"This kind of risk estimate could eventually help people and their doctors decide when to begin therapy or make lifestyle changes that may delay the onset of symptoms. It's similar to how cholesterol levels help predict heart attack risk," says Ronald Petersen, M.D., Ph.D., neurologist and director of the Mayo Clinic Study of Aging, who is a co-author of the study.

The research stands apart because it draws from the Mayo Clinic Study of Aging, a long-running effort in Olmsted County, Minnesota, that tracks thousands of residents over time. The analysis for this study included data from 5,858 participants. Unlike most studies, Mayo researchers are able to continue following participants even after they stop actively taking part, using medical record data — ensuring nearly complete information about who develops cognitive decline or dementia.

"This gives us a uniquely accurate picture of how Alzheimer's unfolds in the community," says Terry Therneau, Ph.D., who led the statistical analysis and is the senior author of the study. "We found that the incident rate of dementia was two times greater among the people who dropped out of the study than those who continued to participate."

The study elevates the significance of MCI, which is the stage targeted by current Alzheimer's drugs that slow but do not stop progression.

While the new tool is currently a research instrument, it represents a major step toward more personalized care. Future versions may incorporate blood-based biomarkers, which could make testing more accessible.

The work was supported by the National Institute on Aging, the GHR Foundation, Gates Ventures and the Alexander Family Foundation.

The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.

"Ultimately, our goal is to give people more time — time to plan, to act and to live well before memory problems take hold," says Dr. Petersen.

Review the study for a complete list of authors, disclosures and funding.

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic scientists create tool to predict Alzheimer’s risk years before symptoms begin appeared first on Mayo Clinic News Network.