ROCHESTER, Minn. — A liver disease affecting nearly 30% of adults worldwide is not a single illness but five biologically distinct subtypes, Mayo Clinic researchers have found. Each carries different risks for heart disease, liver failure, cancer and the need for liver transplantation.

The study, published in Nature Communications and conducted in collaboration with scientists at Virginia Tech, shows that metabolic dysfunction-associated steatotic liver disease has multiple pathways — some tied to obesity and diabetes, others driven by inherited genetic factors.

Notably, genetic subtypes are associated with a higher risk of progression to advanced liver disease, including in patients without typical metabolic risk factors.

The findings could help identify high-risk patients earlier and guide more precise screening and personalized treatment.

"When clinical and genomic data are analyzed together at this scale, you begin to see patterns of disease progression that would otherwise remain hidden," says Shulan Tian, Ph.D., co-senior author and a bioinformatician at Mayo Clinic. "Once you separate these subtypes, you can start to match treatments to the biology that's actually driving the disease."

Metabolic dysfunction-associated steatotic liver disease, formerly called nonalcoholic fatty liver disease, occurs when fat builds up in the liver. It often develops without symptoms but can progress to inflammation, scarring and irreversible damage. It is a leading cause of cirrhosis, liver cancer and transplantation worldwide.

Decoding liver disease at scale

To uncover these subtypes, researchers integrated genetic sequencing with detailed clinical data from more than 4,600 patients with the disease. The dataset spanned a wide range of measures — from liver enzymes, body mass index and lipid levels to coexisting conditions such as diabetes, depression and sleep apnea.

Using advanced computational modeling, the team identified groups of patients who shared underlying biological signals, defining distinct subtypes of the disease.

"What's emerging here is a way to systematically identify meaningful subgroups within complex disease," says Eric Klee, Ph.D., co-senior author and the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation. "It helps us map complex disease with such precision that we can begin to anticipate its course and intervene before the most serious damage occurs."

The discovery was powered by Mayo Clinic's Research Data Atlas, a platform that connects genetic data with patient records to reveal patterns across large populations — a system Dr. Klee helped build. A key component of the Atlas is the Tapestry Study, which has generated Mayo Clinic's largest collection of exome data from more than 100,000 participants. The dataset captures key genetic information that shapes how diseases develop and progress.

"This is exactly the kind of insight large-scale genomic research was built to deliver," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director for the Center for Individualized Medicine who led the Tapestry Study and is a co-author of the research. "When you connect genetic data with detailed clinical information across large populations, you can start to redefine diseases in ways that directly impact patient care."

Liver disease's hidden effects across the body

The study also revealed links beyond the liver. For the first time, researchers found that specific subtypes are associated with conditions such as depression, sleep apnea and migraine, underscoring the disease's broad systemic impact across multiple organ systems.

Next, the team plans to test the approach in broader patient populations and explore how these subtypes respond to different treatments, including therapies such as GLP-1 receptor agonists.

First author Tahmina Sultana Priya, now a Ph.D. student at Virginia Tech, contributed to the research while at Mayo Clinic. 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.

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

The post 5 subtypes of common liver disease discovered — including rapidly progressing genetic forms appeared first on Mayo Clinic News Network.

Mayo Clinic researchers are uncovering the earliest shifts in disease biology — long before symptoms appear — revealing how disease takes root and opening new possibilities to change its course. 

By the time a disease is diagnosed, it may have been developing silently for years. Along the way, the body leaves clues: proteins shift, metabolism changes, immune responses evolve, and environmental exposures leave measurable traces. Until recently, many of these early signals were impossible to detect.

Mayo Clinic researchers are now charting that hidden period between health and disease — a new frontier in medicine that could transform how conditions such as Alzheimer's disease, heart failure, pulmonary fibrosis, chronic liver disease and chronic kidney disease are identified and intercepted before symptoms emerge.

The new Mayo Clinic initiative, called Precure Research, brings together biospecimens, advanced biological data, environmental health research, longitudinal clinical data, wearable technologies and artificial intelligence (AI) to better understand how disease begins, predict risk earlier and create new opportunities for prevention.  

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care."

Dr. Konstantinos Lazaridis

A glimpse of what's possible 

The initiative is already generating discoveries. Mayo Clinic scientists have identified inherited risks for cancer and cardiovascular disease in nearly 2,000 people — many of whom had no previous indication they were at risk. Other studies have shown that certain precancerous changes can be detected years before cancer develops. AI can help clinicians identify signs of pancreatic cancer years before diagnosis, while subtle biological changes linked to Alzheimer's disease begin decades before memory loss. Mayo Clinic researchers are using AI, genetics and wearable technologies to reveal inherited heart disease before heart failure.

"Precure Research marks the beginning of the next era of scientific discovery and its translation into patient care," says Konstantinos Lazaridis, M.D., the Carlson and Nelson Endowed Executive Director of Mayo Clinic's Center for Individualized Medicine and director of Precure Research. "We are building the analytical and clinical tools needed to investigate questions that medicine has long recognized but has not been able to fully answer in ways that directly benefit patients."

The invisible years before diagnosis 

The initiative combines data from genes, proteins, metabolites, clinical records, wearable devices and environmental exposures to create a comprehensive view of how health changes and disease develops over time.

Underlying Precure Research is a new Mayo Clinic research ecosystem designed to study health and disease at an unprecedented scale. The initiative aims to build Mayo Clinic's largest integrated collection of biospecimens and scientific and health data to accelerate disease prediction and prevention.

Biological samples become data, and data becomes insight into the mechanisms of disease. Those insights drive the discovery of new biomarkers and therapies while informing smarter clinical trials.

AI helps researchers power that transformation, analyzing billions of data points simultaneously to reveal patterns that would otherwise remain invisible.

"Genomics showed us the blueprint, the underlying architecture of human biology," Dr. Lazaridis says. "Now we're watching that structure in motion — shifting, adapting, unfolding over time, shaped by the world around us and inside us, ultimately influencing the unique lives we each live." 

A lifetime of exposures

Disease is shaped by more than genetics alone. Across a lifetime, environmental and lifestyle exposures leave biological changes that accumulate over time. Scientists call this the exposome: the sum of those exposures and their effects on human biology.

These influences range from air, water and diet to pollutants, heavy metals, pesticides, physical activity, sleep, stress, noise and light.

"The air we breathe, the food we eat and the places we live leave a biological imprint," Dr. Lazaridis says. "Understanding those accumulated influences is essential to understanding why disease develops in one person and not another."

Researchers can now measure many of these exposures directly in blood and other biospecimens. Early efforts focus on heavy metals, pesticides and microplastics, linking those findings with geographic data to better understand how the places people live may influence their long-term health.

The exposome also captures protective influences, including nutrients and bioactive compounds that may support resilience and regulate inflammation, aging and metabolism.

A new vision for medicine 

The initial focus of Precure Research includes diseases of the brain, heart, kidneys, liver, and lungs, and their intersection with biological pathways such as inflammation, oxidative stress, aging and metabolic dysfunction.

Its long-term aim is to extend healthspan — the number of years people live in good health, free from chronic disease and disability — by addressing the drivers of chronic disease.

Precure Research is part of Mayo Clinic's Bold. Forward. strategy to Cure, Connect and Transform healthcare — helping define a future where disease is identified earlier, understood more completely and intercepted before it takes hold.

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PHOENIX — Researchers have validated a genetic scoring tool that may help physicians diagnose idiopathic pulmonary fibrosis and identify which patients are at greatest risk for severe outcomes, including death or the need for a lung transplant. The findings come from a new international study of more than 570,000 people co-led by Mayo Clinic and Brigham and Women's Hospital.

Published in the American Journal of Respiratory and Critical Care Medicine, the study is one of the largest real-world evaluations of a polygenic risk score for idiopathic pulmonary fibrosis. The findings bring this genomic approach one step closer to clinical care.

"Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

- Dr. Victor Ortega

Researchers analyzed genomic and electronic health record data from four major biobanks in the U.S. and U.K., including the Mayo Clinic Biobank and Mayo Clinic Tapestry. They calculated a polygenic risk score for each participant by combining the effects of more than 60,000 DNA variants associated with idiopathic pulmonary fibrosis. While each genetic variant contributes only a small amount of risk, together they reveal patterns of inherited susceptibility that would otherwise be difficult to detect.

The researchers then tested whether the score could identify patients with the disease and predict clinical outcomes.

People with high polygenic risk scores were nearly three times more likely to have the disease than those with lower scores. The genetic score became even more predictive as researchers applied increasingly specific definitions of the disease, suggesting the score may one day help distinguish idiopathic pulmonary fibrosis from other forms of interstitial lung disease.

Among patients with the disease, those with high genetic risk were 23% more likely to die or require a lung transplant, indicating the score may also help identify patients at greatest risk of poor outcomes.

"Every patient has a unique genetic blueprint that we can use to estimate risk for the development of disease," says Victor Ortega, M.D., Ph.D., a pulmonologist, associate director of Mayo Clinic's Center for Individualized Medicine in Arizona, and a co-senior author of the study. "Polygenic risk scores add a new layer of biological insight into the prediction of pulmonary fibrosis and mortality outcomes, bringing us closer to a future where diagnosis, prognosis and treatment are informed by each patient's unique molecular signatures."

"Showing that this approach works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

- Dr. Christopher Grilli

Idiopathic pulmonary fibrosis causes irreversible scarring of the lungs that progressively limits a person's ability to breathe. More than 100,000 Americans are living with the disease, and an estimated 30,000 to 40,000 new cases are diagnosed each year, according to the National Institutes of Health.

Because its symptoms often resemble those of other interstitial lung diseases, diagnosis can be delayed until significant, irreversible lung damage has already occurred. Confirming the diagnosis sometimes requires an invasive lung biopsy to collect lung tissue. Researchers hope a noninvasive genetic test using DNA from a blood or saliva sample may help reduce the need for those procedures in selected patients.

"Most polygenic risk scores are developed in carefully selected research populations," says Christopher Grilli, Pharm.D., a researcher at Mayo Clinic's Center for Individualized Medicine and co-first author of the study. "Showing that this approach also works across more than half a million people receiving routine clinical care is an important step toward understanding how it can ultimately benefit patients."

If further validated, researchers envision genomic risk scores complementing imaging and other diagnostic tools to help physicians diagnose the disease with greater confidence.

This research aligns with Mayo Clinic's Precure Research initiative, which seeks to uncover the earliest biological changes associated with disease and translate those discoveries into clinical tools that improve diagnosis, personalize care and ultimately change the course of disease. As part of that effort, the Precure-Lung study, led by Dr. Ortega, is expanding Mayo Clinic's research into interstitial lung diseases, including idiopathic pulmonary fibrosis.

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:  

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

The post Researchers chart a genetic path to diagnosing pulmonary fibrosis and predicting outcomes appeared first on Mayo Clinic News Network.

The findings offer new insight into how the immune system and gut microbiome interact in this chronic condition and point to potential new therapeutic strategies.

IBD, which includes Crohn's disease and ulcerative colitis, affects millions of people worldwide. The condition is driven in part by the immune system reacting to normally harmless bacteria in the gut, reflecting a breakdown in what is known as immune tolerance. Symptoms of ulcerative colitis and Crohn's disease usually include belly pain, diarrhea, rectal bleeding, extreme tiredness and weight loss.

While many current therapies focus on reducing inflammation, less is understood about how to restore balanced interactions between the immune system and the gut microbiome.

"This study suggests vitamin D may help rebalance how the immune system sees gut bacteria," says lead author John Mark Gubatan, M.D., a gastroenterologist at Mayo Clinic in Florida. "That's an important step toward understanding how we might restore immune tolerance in IBD."

In the study, researchers evaluated 48 people with IBD who had low vitamin D levels. Participants received weekly vitamin D supplements for 12 weeks. Blood and stool samples collected before and after treatment were analyzed using advanced sequencing to map interactions between immune responses and the gut microbiome.

Vitamin D supplementation was associated with increased levels of immunoglobulin A (IgA), which is typically linked to protective immune responses, and decreased levels of immunoglobulin G (IgG), more often associated with inflammation. The researchers also observed changes in immune signaling pathways and increased activity of regulatory immune cells that help control inflammation.

Together, these findings suggest vitamin D may help promote a more balanced, protective immune response to the gut microbiome.

Vitamin D supplementation was also associated with improvements in disease activity scores and a stool-based marker of inflammation. However, the researchers emphasize the study was small and not designed to establish cause and effect.

"We saw encouraging signals, but this was not a randomized trial," Dr. Gubatan says. "These findings need to be confirmed in larger, controlled studies."

The researchers caution that patients should not change their vitamin D use without medical guidance.

“Vitamin D is widely available, but dosing needs to be individualized, especially in patients with chronic inflammation,” Dr. Gubatan adds. “Patients should work with their healthcare team.”

This work was supported by a grant from Doris Duke Physician Scientist Fellowship Award (Grant #2021091), Chan Zuckerberg Biohub Physician Scientist Scholar Award, and National Institutes of Health (NIH) NIDDK LRP Award (2L30 DK126220). For a complete list of authors, disclosures and funding, see 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:

• Sharon Theimer, Mayo Clinic Communications, newsbureau@mayo.edu

The post Vitamin D linked to immune response to gut microbiome in inflammatory bowel disease 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.

Early in his medical training, Sarosh Irani, B.M., B.Ch., D.Phil., met a patient who would change the course of his career. The woman, in her mid-30s, arrived at the hospital confused, trembling and wracked by seizures. She was losing her memory and her ability to walk. Yet unlike many with such severe neurological decline, she recovered completely.

Her turnaround came after the clinical team discovered a particular antibody in her blood — proof that her immune system had attacked her brain. When they suppressed that immune response, her symptoms disappeared. The discovery not only changed that woman's life but also opened a window into a new, potentially reversible, facet of medicine — one in which the immune system itself could explain devastating brain diseases.

That revelation propelled Dr. Irani into a field that bridges neurology and immunology, one that continues to expand today from his laboratory at Mayo Clinic in Florida.

A burgeoning field

Dr. Irani's first passion was psychiatry. "I wanted to understand disorders of the mind," he recalls. But he found that the field lacked the molecular footholds that could make its mysteries scientifically tractable. “You couldn't put your hands on the biology,” he says. "There were too many inferences and not enough mechanisms."

He turned to neurology just as scientists were discovering that neurological conditions could, in fact, be autoimmune diseases.

Dr. Irani joined, and subsequently led, the University of Oxford's autoimmune neurology lab, where he helped identify several antibodies that define distinct syndromes — including the antibodies LGI1 and CASPR2, now standard diagnostic markers for treatable forms of various autoimmune neurological conditions.

"What was once a medical curiosity has become a thriving field," says Dr. Irani, who came to Mayo Clinic in 2023. "Twenty years ago, there were no known antibodies affecting the brain. Now we know 20 or 30 such antibodies, and each one represents a potential cure."

Toward Precure

For Irani, these discoveries connect directly to Mayo Clinic's Precure initiative, which aims to predict and prevent disease before symptoms appear. "There are very few examples in medicine where we have a tractable handle on what's causing the disease," he explains. "Here we know the antibodies cause the disease. So the question is simple: How and why are they made? If we can work out causation, we can get close to pre-cure."

His lab is tackling that question through two complementary approaches: exploring patients' genetic predispositions and studying their immune cells. One variant, for example — in an HLA gene involved in presenting proteins to the immune system — appears in more than 90 percent of patients with a particular autoimmune neurological condition.

But genes alone do not tell the whole story. Irani suspects that environmental triggers, such as infections or even medications, act as the final push. "It's likely a multi-hit process," he says. "You need the gene, a misbehaving immune cell and an environmental spark."

His lab is studying patients' own immune cells to trace where this autoimmune process begins. Evidence increasingly points to the periphery, not the brain, as the starting point. That idea is supported by emerging research on the brain's lymphatic drainage system, which helps clear waste and immune molecules.

Early clues to autoimmunity

Recently, Dr. Irani and colleagues showed that biomarkers of neurodegeneration can be detected in the lymph nodes of the neck. These lymph nodes drain byproducts and proteins resulting from brain activity via a network of tiny lymphatic vessels.

Using ultrasound-guided fine-needle aspiration — a quick sampling technique similar to drawing blood — the team measured several proteins including amyloid beta and tau, proteins that build up in Alzheimer's disease, as well as other markers of brain cell health. They found that almost all of these proteins were found in much higher quantities in the lymph nodes than in the blood, especially one called phosphorylated tau (pTau181), which was 266 times more concentrated.

Strikingly, pTau181 levels in lymph nodes decreased with age, suggesting that the brain's ability to clear toxic proteins through lymphatic drainage declines over time — potentially contributing to diseases like Alzheimer's. The discovery also challenges one of medicine's oldest assumptions: that the brain is "immune-privileged" and largely sealed off from the body's immune system.

"This is the first direct evidence that brain proteins accumulate in cervical lymph nodes in living people," says Dr. Irani. "It opens up a minimally invasive way to study how the brain clears waste — and how that process falters with age."

Lymph node aspiration is far less invasive than spinal taps, yet it could offer powerful insight into brain health, aging, and disease progression.

Brain on fire

Dr. Irani's research has come full circle with a new study in The Lancet Psychiatry. The research focuses on patients with autoimmune encephalitis — a condition popularized by the book and movie "Brain on Fire"— whose illnesses often first appear to be psychiatric. The work shows that these patients can be distinguished from others by a simple scoring system based on how rapidly symptoms appear and how they evolve.

"It's a mixture of symptoms — depression, anxiety, psychosis, sleep and eating disturbances — all unfolding over days," he says. "If clinicians recognize that pattern early, we can treat it before irreversible brain injury occurs."

Current therapies for autoimmune encephalitis rely on broad immunosuppression — powerful drugs that quiet the entire immune system and leave patients vulnerable to infection. Dr. Irani envisions a more refined approach that involves the selective silencing of only the harmful immune cells while preserving the rest.

"We want to pick off just the bits causing trouble," he says. "If we can identify exactly what the immune system is attacking, we can teach it tolerance only to that target."

That vision, he believes, could extend to other conditions where the immune system plays a role, potentially informing treatments for dementia, cancer and even common psychiatric disorders. "We're trying to translate these observations to more widespread diseases," he says. "There's enormous potential."

The post Mayo Clinic researcher redefines the brain’s immune connection appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — At Mayo Clinic, cardiologists Peter Noseworthy, M.D., and John Giudicessi, M.D., Ph.D., are uncovering the earliest signs of a genetic heart condition that often strikes without warning. Their work shows that early detection, and even prevention, may be possible long before symptoms appear. 

The condition, arrhythmogenic right ventricular cardiomyopathy, weakens the molecules that hold heart cells together. As those bonds deteriorate, healthy muscle is replaced with scar tissue and fat, leaving the heart weaker.  

The disease often advances silently. Sometimes the first sign is when a person suddenly collapses during exercise. For many, a diagnosis comes only after the heart is already damaged. Detecting it earlier could spare patients from heart failure, the need for a transplant or sudden death. 

"We spend so much time managing the consequences of this disease — ablations, transplants, repeated hospitalizations. It's a much better paradigm to ask: What can we do to prevent this in the first place?" 

"We spend so much time managing the consequences of this disease — ablations, transplants, repeated hospitalizations," Dr. Noseworthy says. "It's a much better paradigm to ask: What can we do to prevent this in the first place?" 

Leading a new era of heart care 

Dr. Noseworthy leads Mayo Clinic's Division of Heart Rhythm Services, where he cares for patients with heart rhythm disorders and helps guide innovation strategies across the institution. Much of his research centers on using digital tools and artificial intelligence (AI) to detect problems earlier and improve patient care. 

Dr. Giudicessi, a genetic cardiologist, focuses on inherited heart rhythm conditions and how genetic changes influence who develops disease. His work bridges patient care and laboratory research, including first-in-human clinical trials that explore the potential of gene therapy. 

Together, they turned to two powerful data sources: the genetic code that shapes the heart and the electrical signals that guide its rhythm. 

"So much of medicine is reactionary — we wait for something bad to happen. This work is ushering in the tools to push against disease and to identify it early." 

Pinpointing risk in genes and rhythm  

Their search for answers started in Mayo Clinic's new Research Data Atlas, which unites decades of genetic, clinical and biospecimen data. Within it, they identified people carrying disease-causing mutations in PKP2, the gene most often linked to this disease.  

About 1 in 2,000 people carry a mutation in the PKP2 gene, but many never develop the disease. The challenge is knowing who will — and stepping in early enough to change the outcome. That question drives Dr. Giudicessi's work. 

"So much of medicine is reactionary — we wait for something bad to happen," Dr. Giudicessi says. "This work is ushering in the tools to push against disease and to identify it early." 

To spot those early rhythm changes, the team drew on an AI model developed by Mayo Clinic cardiologist Ammar Killu, M.B.B.S., and his team.  

Analyzing electrocardiograms from patients with a PKP2 mutation, the AI helped the researchers identify faint patterns that marked the first signs of disease.  

"This research shows how AI can help us identify really subtle changes that may facilitate earlier diagnosis and then allow us to move beyond individual cases to understand patterns across populations."

"This research shows how AI can help us identify really subtle changes that may facilitate earlier diagnosis and then allow us to move beyond individual cases to understand patterns across populations," Dr. Killu says. "It's a powerful example of how we can scale early detection to reach more patients before disease takes hold." 

Those insights led to a next step. Guided by the AI findings, Dr. Noseworthy and Dr. Giudicessi provided smartwatches to people who were showing early signs of disease. The devices help track daily activity levels — important data, since strenuous exercise can accelerate the disease, while even small adjustments may help slow it. 

The researchers are also exploring gene therapy for PKP2. Still in early testing, the approach may one day restore the missing gene and keep the disease from advancing. 

Building medicine's next chapter 

Their work is part of a larger shift at Mayo Clinic: predicting and preventing disease before it takes hold. That vision drives Precure, an initiative to intercept serious conditions early enough to alter their course. With tools like the Research Data Atlas, investigators can study health patterns across large populations, detect risk sooner and potentially guide people to care before disease advances. 

For Dr. Noseworthy, Dr. Giudicessi and Dr. Killu, the vision is bigger than a single study. They are helping build the infrastructure to move medicine earlier in the course of disease, where illness can be intercepted at scale. 

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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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At the first U.S. 'Undiagnosed Hackathon,' scientists from around the world will team up at Mayo Clinic to solve unsolved medical mysteries. 

Young Julian Limon clutches his blanket wherever he goes, a source of comfort during hospital stays, procedures and tests. At 17 months, he has not yet reached walking or talking milestones. His brittle hair and unexplained neurological symptoms compound his challenges. He has endured pneumonia and other respiratory illnesses, and his weak immune system leaves him vulnerable. Despite extensive evaluations and genetic testing, Julian's condition remains a mystery.

This September, Julian's family will travel to Mayo Clinic in Minnesota to take part in the Undiagnosed Hackathon, a global effort to solve rare diseases that have long gone unexplained. 

The Hackathon was inspired by Helene and Mikk Cederroth, founders of the Wilhelm Foundation, who lost two young sons and a daughter to an undiagnosed condition. Their grief became a call to action. Over the past two decades, they've built a global network of scientists, clinicians and advocates committed to finding answers. 

An unprecedented collaboration

Over three days at Mayo Clinic, more than 125 scientists, clinicians and AI experts will gather for the first U.S.-based Undiagnosed Hackathon. They will come from 30 countries across six continents. Their goal: to uncover answers for Julian and 28 others whose conditions have eluded diagnosis. 

Having families in person at the Hackathon allows researchers to observe traits and ask questions that data alone can't capture. 

"If you put a molecular biologist next to a bioinformatician next to a clinician who have come from different parts of the world, each will bring a unique lens to the same investigation shaped by their training and lived experience," Dr. Klee says. "That's how breakthroughs happen." 

Unlocking hidden clues with advanced tools 

Among the international team are Mayo Clinic's Dr. Cherisse Marcou, assistant professor and co-director of the Clinical Genomics laboratory, and Dr. Eric Klee, the Everett J. and Jane M. Hauck Midwest Associate Director of Research and Innovation. After participating in last year’s Undiagnosed Hackathon in the Netherlands, they return with momentum to co-lead this year’s event. 

Working with global colleagues, they’ll explore DNA, RNA and other signals using tools that reveal what standard tests can miss. This includes examining long DNA stretches, studying RNA to see which genes are active and identifying chemical changes that turn genes on or off — a process called methylation.

This complex approach, known as omics, combines layers of biological information to better understand how the body works and why disease occurs. Bringing multiple omics together is more like a moving picture than a still photo, where hidden patterns emerge. Artificial intelligence will help scientists integrate these layers and interpret the results.

Breaking silos to spark breakthroughs 

"I come from a place where many families are not afforded the access to the latest and greatest diagnostic testing options in their diagnostic journey," Dr. Marcou says. "To be part of something that brings hope worldwide is deeply personal."

The idea behind the Hackathon is bringing people together who might not otherwise work side by side. 

"If you put a molecular biologist next to a bioinformatician next to a clinician who have come from different parts of the world, each will bring a unique lens to the same investigation shaped by their training and lived experience," Dr. Klee says. "That's how breakthroughs happen." 

Fueled by passion, and personal connection 

Now in its third year, the Hackathon has become a global engine for rare disease discovery. The Cederroths have co-led every one. 

"They've poured their lives into this mission," Dr. Marcou says. "Their energy is transformative. You leave the Hackathon changed." 

For Dr. Marcou, the work is personal. She grew up in the Bahamas, where access to advanced diagnostics is limited. 

"I come from a place where many families are not afforded the access to the latest and greatest diagnostic testing options in their diagnostic journey," she says. "To be part of something that brings hope worldwide is deeply personal." 

Dr. Marcou clinically interprets and decodes genomic data to deliver real-time insights for patients every day and has been involved in the development of AI tools at Mayo Clinic to advance this work. Dr. Klee, a leader in rare disease research, is building the Research Data Atlas to accelerate discoveries by unifying Mayo Clinic's extensive research data. 

Hope for families, and ripple effects worldwide

The Hackathon's goal is ambitious: solve as many cases as possible. Last year, 10 of 26 participants received diagnoses, with promising leads for nine more. One person's diagnosis can also unlock recognition, testing and potential treatment options for others with the same condition. 

"Our ultimate goal is to find answers for all our participants. That said, if we can find an answer for even one person, that would be amazing. If we find answers for 10 or 12 participants, that would be incredible," Dr. Klee says. "And for the participants where a clear answer eludes us, we hope to find strong leads that guide future research and testing for others." 

The Hackathon doesn't end when the event does. The findings must be clinically confirmed before they become diagnoses. For those who receive answers, the next goal is treatment, if one exists. For cases that remain unsolved, the work continues. 

It's also a powerful exchange of knowledge. Collaborators from places with fewer resources gain exposure to advanced techniques, while all experts have the opportunity to learn new approaches from those working alongside them. 

"It's peer-to-peer learning at its best," Dr. Marcou says. "We're all better for it." 

Julian's diagnostic journey

Even after long days of doctor visits and tests, Julian still breaks into bright smiles. He is working with physical therapists to build strength as his family continues to hope for a diagnosis. 

"I feel incredibly grateful that we'll have so many experts looking closely at Julian," says his mother, Jasmine Limon. "I just want to know what we're facing so we can give him the best possible care." 

At its heart, the Hackathon is where some of the world's brightest minds gather around families like Julian's, determined to give all they can and to open new doors in medicine. 

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ROCHESTER, Minn. — Mayo Clinic researchers have developed a new artificial intelligence (AI) tool that helps clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using a single, widely available scan — a transformative advance in early, accurate diagnosis. 

The tool, StateViewer, helped researchers identify the dementia type in 88% of cases, according to research published online on June 27, 2025, in Neurology, the medical journal of the American Academy of Neurology. It also enabled clinicians to interpret brain scans nearly twice as fast and with up to three times greater accuracy than standard workflows. Researchers trained and tested the AI on more than 3,600 scans, including images from patients with dementia and people without cognitive impairment. 

This innovation addresses a core challenge in dementia care: identifying the disease early and precisely, even when multiple conditions are present. As new treatments emerge, timely diagnosis helps match patients with the most appropriate care when it can have the greatest impact. The tool could bring advanced diagnostic support to clinics that lack neurology expertise. 

The rising toll of dementia 

Dementia affects more than 55 million people worldwide, with nearly 10 million new cases each year. Alzheimer's disease, the most common form, is now the fifth-leading cause of death globally. Diagnosing dementia typically requires cognitive tests, blood draws, imaging, clinical interviews and specialist referrals. Even with extensive testing, distinguishing conditions such as Alzheimer's, Lewy body dementia and frontotemporal dementia remains challenging, including for highly experienced specialists. 

StateViewer was developed under the direction of David Jones, M.D., a Mayo Clinic neurologist and director of the Mayo Clinic Neurology Artificial Intelligence Program.  

"Every patient who walks into my clinic carries a unique story shaped by the brain's complexity," Dr. Jones says. "That complexity drew me to neurology and continues to drive my commitment to clearer answers. StateViewer reflects that commitment — a step toward earlier understanding, more precise treatment and, one day, changing the course of these diseases." 

To bring that vision to life, Dr. Jones worked alongside Leland Barnard, Ph.D., a data scientist who leads the AI engineering behind StateViewer. 

"As we were designing StateViewer, we never lost sight of the fact that behind every data point and brain scan was a person facing a difficult diagnosis and urgent questions," Dr. Barnard says. "Seeing how this tool could assist physicians with real-time, precise insights and guidance highlights the potential of machine learning for clinical medicine." 

Turning brain patterns into clinical insight 

The tool analyzes a fluorodeoxyglucose positron emission tomography (FDG-PET) scan, which shows how the brain uses glucose for energy. It then compares the scan to a large database of scans from people with confirmed dementia diagnoses and identifies patterns that match specific types, or combinations, of dementia. 

Alzheimer's typically affects memory and processing regions, Lewy body dementia involves areas tied to attention and movement, and frontotemporal dementia alters regions responsible for language and behavior. StateViewer displays these patterns through color-coded brain maps that highlight key areas of brain activity, giving all clinicians, even those without neurology training, a visual explanation of what the AI sees and how it supports the diagnosis. 

Mayo Clinic researchers plan to expand the tool's use and will continue evaluating its performance in a variety of clinical settings. 

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 

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Editor's note: May is National Cancer Research Month, and May 20 is Clinical Trials Day.

A cancer diagnosis is an emotional experience. Learning that you have cancer can create feelings of hopelessness, fear and sadness. This is especially true if your cancer is advanced or available treatments are unable to stop or slow its growth.

"Often, when patients are diagnosed with cancer, they feel hopeless and scared. Clinical trials are one way patients can be proactive. They can make a choice in how their care is going to be," says Matthew Block, M.D., Ph.D., a Mayo Clinic medical oncologist.

Cancer clinical trials help physician-scientists test new and better ways to control and treat cancer. During a clinical trial, participants receive specific interventions, and researchers determine if those interventions are safe and effective. Interventions studied in clinical trials might be new cancer drugs or new combinations of drugs, new medical procedures, new surgical techniques or devices, new ways to use existing treatments, and lifestyle or behavior changes.

Clinical trials provide access to potential treatments under investigation, giving options to people who otherwise may face limited choices. "Clinical trials open the door to a new hope that maybe we can fight their cancer back and give them a better quality of life," says Geoffrey Johnson, M.D., Ph.D., a Mayo Clinic radiologist, nuclear medicine specialist and co-chair of the Mayo Clinic Comprehensive Cancer Center Experimental and Novel Therapeutics Disease Group.

You will receive cancer treatment if you participate in a clinical trial. "I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment," says Judy C. Boughey, M.D., a Mayo Clinic surgical oncologist, chair of Breast and Melanoma Surgical Oncology at Mayo Clinic in Rochester, Minnesota, and chair of the Mayo Clinic Comprehensive Cancer Center Breast Cancer Disease Group.

"I think one common misperception about clinical trials is that if you enter a clinical trial, you may not get treatment (receive a placebo). And that's actually very much not true. Most clinical trials are looking at one treatment compared to another treatment."Judy C. Boughey, M.D.

Watch this video to hear the experiences of people who have participated in cancer clinical trials and to hear Drs. Block, Johnson and Boughey discuss the importance of clinical trials in cancer care:

Clinical trials are a significant part of cancer care at Mayo Clinic Comprehensive Cancer Center. Cancer care teams work together across specialties to make sure the right clinical trials are available to serve the needs of people with cancer who come to Mayo Clinic.

"We are very particular in how we select the clinical trials that we have available for patients," says Dr. Boughey. "We want to have the best trials available for our patients. Some of the clinical trials are evaluating drugs — we are so excited about those drugs, but we can't prescribe those drugs for patients without having that trial. And so we will actually fight to try to get that trial open here to have it available as an opportunity for our patients."

If you choose to participate in a clinical trial, you will continue to receive cancer care. "For most patients that we evaluate, there's always the standard of care treatment option for those patients. And then, in many situations, there's also a clinical trial that the patient can participate in," says Dr. Boughey.

People who participate in clinical trials help make new and better cancer care available for future patients. The treatments available for cancer patients today exist because of the clinical trial participants of yesterday. "We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit," says Dr. Johnson.

"We couldn't advance medicine if it wasn't for people volunteering for trials. And the promise from our side is to say we're not going to put patients on trials or offer trials for them to consider unless we think there's a good chance that they'll get a benefit or that society at large will get a benefit."Geoffrey Johnson, M.D., Ph.D.

Participating in a clinical trial may give you access to cutting-edge treatment, improve your quality of life and extend your time with loved ones.

"It's definitely worth reaching out to your healthcare provider and asking, 'What clinical trials could I be a potential candidate for?'" says Dr. Boughey. "And remember, you can ask this of your surgical oncologist, your medical oncologist, your radiation oncologist, or any of the physicians you're seeing because there are trials in all disciplines. There are also ongoing trials that require the collection of tissue or the donation of blood. They can also be important in trying to help future generations as we continue to work to end cancer."

Participating in a clinical trial is an important decision with potential risks and benefits. Explore these FAQ about cancer clinical trials, and ask your care team if a clinical trial might be right for you.

This article first published on the Mayo Clinic Comprehensive Cancer Center blog.

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