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

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ROCHESTER, Minn. — When it comes to treating disease, one promising avenue is addressing the presence of senescent cells. These cells — also known as "zombie cells" — stop dividing but don't die off as cells typically do. They turn up in numerous diseases, including cancer and Alzheimer's disease, and in the process of aging. While potential treatments aim to remove or repair the cells, one hurdle has been finding a way to identify them among healthy cells in living tissue. 

In the journal Aging Cell, Mayo Clinic researchers report finding a new technique to tag senescent cells. The team used molecules known as "aptamers" — small segments of synthetic DNA that fold into three-dimensional shapes. Aptamers have the ability to attach themselves to proteins on the surfaces of cells. In mouse cells, the team found several rare aptamers, identified from among more than 100 trillion random DNA sequences, that can latch onto specific cell surface proteins and flag senescent cells.

"This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones," says biochemist and molecular biologist Jim Maher, III, Ph.D., a principal investigator of the study. "Though this study is a first step, the results suggest the approach could eventually apply to human cells."

From a quirky idea to collaboration  

The project began with the quirky idea of a Mayo Clinic graduate student who had a chance conversation with a classmate.

Keenan Pearson, Ph.D. — who recently received his degree from Mayo Clinic Graduate School of Biomedical Sciences — was working under the mentorship of Dr. Maher, studying how aptamers might address neurodegenerative diseases or brain cancer.

A few floors away, Sarah Jachim, Ph.D., — who was also then conducting her graduate research — was working in the lab of researcher Nathan LeBrasseur, Ph.D., Director, Mayo Clinic Robert and Arlene Kogod Center on Aging, who studies senescent cells and aging.

At a scientific event, the two happened to chat about their graduate thesis projects. Dr. Pearson thought aptamer technology might be able to identify senescent cells. "I thought the idea was a good one, but I didn't know about the process of preparing senescent cells to test them, and that was Sarah's expertise," says Dr. Pearson, who became lead author of the publication.  

They pitched the idea to their mentors and to researcher Darren Baker, Ph.D., who investigates therapies to treat senescent cells. At first, Dr. Maher acknowledges, the students' idea seemed "crazy" but worth pursuing. The three mentors were excited about the plan. "We frankly loved that it was the students' idea and a real synergy of two research areas," says Dr. Maher.

The students obtained compelling results sooner than they expected and quickly recruited other student participants from the labs. Then-graduate students Brandon Wilbanks, Ph.D., Luis Prieto, Ph.D., and M.D.-Ph.D. student Caroline Doherty, each contributed additional approaches, including special microscopy techniques and more varied tissue samples. "It became encouraging to expend more effort," Dr. Jachim says, "because we could tell it was a project that was going to succeed."

Identifying attributes of senescent cells

 The study has provided new information about senescent cells beyond a way to tag them. "To date, there aren't universal markers that characterize senescent cells," says Dr. Maher. "Our study was set up to be open-ended about the target surface molecules on senescent cells. The beauty of this approach is that we let the aptamers choose the molecules to bind to."

The study found several aptamers latched onto a variant of a specific molecule on the surface of mouse cells, a protein called fibronectin. The role of this variant fibronectin in senescence is not yet understood. The finding means that aptamers may be a tool to further define unique characteristics of senescent cells.

Additional studies will be necessary to find aptamers that can identify senescent cells in humans. Aptamers with the ability to latch onto senescent cells could potentially deliver a therapy directly to those cells. Dr. Pearson notes aptamer technology is less expensive and more versatile than conventional antibodies, proteins that are typically used to differentiate cells from one another.

"This project demonstrated a novel concept," says Dr. Maher. "Future studies may extend the approach to applications related to senescent cells in human disease."

See 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:

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

The post A new tool to find hidden ‘zombie cells’ appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — The immune system is meant to protect the body from infection and disease. But with age, it can become less capable of doing so. However, 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 are studying why some individuals have a 'fountain of youth' in their immune systems. We want to learn from them," says Cornelia Weyand, M.D., Ph.D., a Mayo Clinic rheumatologist and clinician-scientist. She is a lead author on a perspective paper published in Nature Aging.

Dr. Weyand's research team discovered this cellular fountain of youth in more than 100 older patients who came to Mayo Clinic to receive treatment for an autoimmune disease that affects the arteries, including the aorta, called giant cell arteritis. Dr. Weyand and colleagues found in the diseased tissue of these patients specialized immune cells, called stem-like T cells. These immune cells behave like young stem cells that usually regenerate and aid healing and growth; but in this case, they were spreading the disease. This team of researchers also discovered autoimmune stem cells in humans previously.

"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," she says.

Autoimmunity is when the immune system mistakenly attacks healthy tissues and organs.

In addition, the researchers saw that the immune checkpoint inhibitors that regulate the immune system were not working properly.

Benefits of immune system aging

"Contrary to what one may think, there are benefits to having an immune system that ages in tandem with the body," says Jörg Goronzy, M.D., Ph.D., a Mayo Clinic researcher on aging who is a co-lead author of the paper. "We need to consider the price to pay for immune youthfulness. That price can be autoimmune disease."

Immune aging is a sophisticated adaptation mechanism that the immune system can use to prevent autoimmune disease, say the researchers.

They are in the process of developing new diagnostic tests that will help find patients and healthy individuals who carry high numbers of immune stem cells and may be predisposed to autoimmune disease later in life. 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. 

Additional resources:
Mayo Clinic advances research on mysterious blood vessel disease

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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:

• Alison Satake, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic researchers discover the immune system’s ‘fountain of youth’ appeared first on Mayo Clinic News Network.

For Anthony Maita, 'Buddy' is not just any other dog.

"He's the best thing that's ever happened to me," says Anthony.

It's no wonder, considering Buddy was right by Anthony's side during one of the most challenging times of his life — when Anthony began having epileptic seizures.

Watch: When seizures don't stop: Anthony's battle against drug-resistant epilepsy

Journalists: Broadcast-quality video (2:38) is in the downloads at the end of this post. Please courtesy: "Mayo Clinic News Network." Read the script.

"I started having the seizures, noticeable seizures, and from there, it just started getting worse and worse," recalls Anthony.

It began after Anthony graduated from high school. He was making plans for his future and looking forward to attending college. That's when the seizures began.

Initially, the seizures were mild but quickly became more severe. "The experience (seizure) is like a loss of time, like a blank spot in your memory — like you're waking up without any recollection of what happened," says Anthony.

"The seizures were several times a week. His lips would be blue. His mouth would be blue," says Patricia Maita, Anthony's mother. "It so hard to see your child go through that and feel so helpless."

Doctors tried to manage Anthony's seizures with medication, but nothing worked. Eventually Anthony was diagnosed with drug-resistant epilepsy, or DRE.

In search of hope, Anthony's family turned to Mayo Clinic in Arizona.

"Up to a third of patients who develop epilepsy during their life will become resistant to medication," explains Jonathon J. Parker, M.D., Ph.D., a neurosurgeon at Mayo Clinic who specializes in treating the most serious and complex cases of epilepsy, including DRE.

"These patients have tried at least two medications, and they're still having seizures. At that point, we know the chances of seizure freedom unfortunately become very low, and that's when we start looking at other options," says Dr. Parker.

A battle for millions worldwide

Anthony is one of approximately 50 million people worldwide diagnosed with epilepsy. It is one of the most common neurological disorders globally. It is characterized by recurrent unprovoked seizures caused by abnormal electrical activity in the brain.

Of those diagnosed with epilepsy, approximately 30%, or 15 million people, are considered medication-resistant. Uncontrolled seizures often rob many people of their ability to live and function independently.

While it is rare, seizures can lead to sudden unexplained death in epilepsy, or SUDEP. "We know that more frequent seizures mean the patient is at higher risk of SUDEP, so that's why we are very aggressive about treating epilepsy with all the tools we have available," says Dr. Parker.

Current treatment options for patients with DRE include surgical procedures such as brain resection to remove a portion of the brain tissue responsible for generating seizures. A less invasive procedure involves laser ablation therapy that pinpoints and destroys abnormal brain tissue. While often effective, these surgical approaches carry the risk of possible side effects, such as memory impairment, motor deficits and speech difficulties. 

Neuromodulation is another surgical approach that uses electrical or magnetic stimulation to interrupt abnormal neural activity without removing brain tissue.

Unlocking new hope for patients

Now, a growing number of scientists across the globe are part of an innovative trend in research, investigating novel ways to treat DRE. It involves the use of regenerative medicine as a "reparative" approach to help the brain heal. 

Dr. Parker is the lead investigator of the first-in-human clinical trial at Mayo Clinic which studies the use of implanted specialized inhibitory brain cells as a potential reparative treatment for DRE. Dr. Parker's clinical trial is underway in Arizona.

Mayo Clinic in Arizona is one of 29 sites nationwide participating in the inhibitory brain cell implant clinical trial for patients with focal epilepsy, where seizures originate in a specific region of the brain. 

Anthony became Mayo Clinic's first patient to undergo the investigational brain cell implant. 

"We use a very minimally invasive technique where we inject the inhibitory cells through a pencil eraser-sized incision in the back of the head. Our hope is that, over time, these cells become part of the brain and help repair the neural circuitry, and reduce or prevent seizures without the side effects," says Dr. Parker. The cells are implanted in a one-time, single-dose procedure.

"Honestly, it was pretty easy," says Anthony. "I had no trouble with it." Anthony was discharged from the hospital the next day.

Doctors say it is still too early to determine whether the brain cell implant was effective, but they are hopeful.

"Anthony has been doing great since the procedure," says Dr. Amy Z. Crepeau, a neurologist at Mayo Clinic. "We have a great deal of optimism in regard to the potential of this brain cell therapy. Developing a safe and effective, minimally invasive treatment that does not carry the possible negative side effects could be a game changer in treating patients with DRE and improving their quality of life."

Tabitha's life-long struggle to control seizures

Tabitha Wilson lives in fear, never knowing when or where the next seizure will strike.

The Florida resident was diagnosed with epilepsy at the age of 2. She was placed on medication that adequately managed her seizures — until the week before her high school graduation. 

"I was 17 years old sitting in history class when the seizure happened," recalls Tabitha. "They had to load me up in an ambulance in front of the whole school."

Tabitha tried new types of medications, but the seizures only got worse.

"I fell down a flight of stairs, burned myself while cooking. I've completely blacked out and don't know where I am or who you are," says Tabitha. She was eventually diagnosed with drug-resistant epilepsy.

Tabitha underwent three brain surgeries to treat her DRE. Still, the seizures continued.

"I'll have good days and bad days. Some days, I'll have two, three, four seizures, back-to-back," says Tabitha.

Her uncontrolled seizures have robbed Tabitha of the ability to live independently. "I can't drive. I can't cook. I can't go swimming alone. I can't take a bath, only a shower and if someone is home with me," says Tabitha.

Watch: Tabitha Wilson shares what it's like to live with drug-resistant epilepsy.

Tabitha turned to Mayo Clinic in Florida where she learned about a clinical trial also investigating the potential of regenerative medicine as a possible treatment for DRE.

Dr. Sanjeet S. Grewal, director of stereotactic and functional neurosurgery at Mayo Clinic, is leading a team of researchers studying the use of implanted stem cells in conjunction with deep brain stimulation for patients like Tabitha.

Deep brain stimulation is one of the most recent FDA-approved methods of neuromodulation therapy for epilepsy. Studies show that patients who undergo deep brain stimulation experience median seizure reduction up to 70% after five years. However, Dr. Grewal says it is uncommon for patients to become seizure-free. 

"Unfortunately, neuromodulation doesn't give us the seizure freedom we want, and that's why we are trying to combine deep brain stimulation with stem cell therapy to see if we can increase the efficacy of neuromodulation," he says. 

Tabitha became the first patient to undergo the investigational treatment. Dr. Grewal says she is also the first person in the world to undergo surgery for deep brain stimulation and receive stem cell therapy in the thalamus in her brain as a potential treatment for DRE. 

Watch: Dr. Sanjeet Grewal, neurosurgeon, explains how Mayo researchers are leading a new trend in research for treating patients with drug-resistant epilepsy.

The clinical trial involves the use of mesenchymal stem cells, a type of adult stem cell that has anti-inflammatory properties. MSCs may also support tissue repair and healing. Further scientific research is needed to confirm their therapeutic potential in the field of regenerative medicine.

The MSCs used in the clinical trial are derived from fat tissue and created at the Human Cell Therapy Laboratory at Mayo Clinic in Jacksonville, Florida under the leadership of Abba Zubair, M.D., Ph.D., a pioneer in cell therapy.

Dr. Zubair's research teams have developed a cost-effective method of producing MSCs for use in potential treatments for conditions such as stroke.

Dr. Zubair has also led innovative research, including sending stem cells to the International Space Station to investigate how microgravity impacts their growth.

"My mission is to discover ways to address problems that patients have been struggling with and find a solution for them.
I believe the future is bright. "

Dr. Abba Zubair, Pioneer in Cell therapy, Mayo Clinic in Florida

Dr. Zubair has several research projects scheduled to launch into space in 2025.

"MSCs are what we call multipotent, meaning they can differentiate into different cell types based on where they're placed. If they are placed near blood vessels, they can become blood vessel types. If they're placed by heart cells, they can become heart cell types," explains Dr. Grewal.

The hope is the MSCs eventually become neural or brain cell types and interact in the part of the brain where the seizures occur. "It's called paracrine signaling, where they're releasing signals to the brain tissue around them and interacting in a way to try to repair that tissue."

Since undergoing the procedure, there has been an improvement in Tabitha's seizure management. However, Dr. Grewal says it is too early to know whether this is due to the deep brain stimulation, stem cells or both. 

Drs. Grewal and Parker say there is still a long road ahead to determine whether these cell therapies are proven safe and effective for patients with DRE. But they agree each day brings them one step closer to a potential treatment or cure for patients like Tabitha and Anthony.

"We've thought about this for generations, we just didn't have these technologies to enable it. Now we do," says Dr. Grewal. "So, whether it's wound healing, neurodegeneration, epilepsy or stroke, there are so many different studies going on investigating the potential of regenerative or reparative therapies."

Related articles

• Mayo Clinic researchers lead transformative shift toward neurorestorative treatment strategies for most severe forms of epilepsy
• Epilepsy Treatment
• Minimally invasive epilepsy treatment
• Mayo Clinic Minute: Demystifying epilepsy
• Epilepsy Surgery
• Laser ablation surgery helps treat young man’s epilepsy

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Alzheimer's disease affects nearly seven million Americans over the age of 65, or 1 in 9 people in this age group, according to the Alzheimer's Association. Symptoms such as memory loss, trouble concentrating and performing familiar tasks, and personality changes start slowly and progress. Researchers have come a long way in understanding Alzheimer's disease and Alzheimer's Disease Related Dementias (AD/ADRD). A new consensus study report, "Preventing and Treating Dementia: Research Priorities to Accelerate Progress," identifies prevention and treatment strategies for the next decade.  

"We need cutting-edge treatments to help improve the lives of patients who are suffering from debilitating symptoms of dementia and prevention for those at risk," says Nilüfer Ertekin-Taner, M.D., Ph.D., chair of the Department of Neuroscience at Mayo Clinic and leader of the Genetics of Alzheimer's Disease and Endophenotypes Laboratory at Mayo Clinic's campus in Florida. "Neurodegenerative diseases not only affect patients but also the friends and family who care for them."

Dr. Ertekin-Taner served on the select ad hoc committee of the National Academies of Sciences, Engineering, and Medicine (NASEM) which conducted a study assessing the state of research on AD/ADRD and outlined critical research priorities for treatment and prevention, as well as potential barriers to progress. The National Institutes of Health, National Institute on Aging, and National Institute of Neurological Disorders and Stroke asked NASEM to form the committee in response to a request from the U.S. Congress to accelerate research into these diseases.

Researchers looked broadly at the field, including basic to translational to clinical research; lifestyle interventions aimed at preventing and treating AD/ADRD; barriers to advancing progress in the field; and the most promising areas of research. The study looked at Alzheimer's disease, frontotemporal dementia, Lewy body dementia and other vascular causes of cognitive impairment and dementia.

The report identified 11 research priorities for further NIH-funded biomedical research, including:

• Developing better tools, including novel biomarker tests and digital assessment technologies, to monitor brain health across the life course and to screen, predict and diagnose AD/ADRD at scale.

• Implementing advances in clinical research methods and tools to generate data from real-world clinical practice settings that can inform future research.

• Identifying factors driving AD/ADRD risk in diverse populations, particularly understudied and disproportionately affected groups, to better understand disease heterogeneity — including molecular subtypes and disparities in environmental exposures — and to identify prevention opportunities and advance health research equity.

• Characterizing the exposome and gene-environment interactions across the life course to gain insights into biological mechanisms and identify opportunities to reduce AD/ADRD risk and increase resilience.

• Integrating innovative approaches and novel tools into the planning, design and execution of studies to accelerate the identification of effective interventions.

• Advancing the development and evaluation of combination therapies (including pharmacological and nonpharmacological approaches) to better address the multifactorial nature of AD/ADRD.

• Evaluating precision medicine approaches for the prevention and treatment of AD/ADRD to better identify interventions likely to benefit specific groups of individuals.

The report calls for breaking down silos for more collaborative, multidisciplinary research; fostering inclusive research to eliminate health disparities; developing innovative funding strategies; and increasing innovation in research through the expansion of public-private partnerships, among others.

"The past decade of research investments in AD/ADRD has led to significant progress in our understanding of these diseases, bringing us closer to treatments," Dr. Taner said. "In the next decade, we must maintain the momentum of research and innovation to translate these advances to cures for millions of patients and caregivers affected by the dementia epidemic."

Note: Dr. Ertekin-Taner will participate in a webinar on Jan. 15 with other committee members to discuss the report.

The post Mayo Clinic contributes to national Alzheimer’s disease research priorities in new report appeared first on Mayo Clinic News Network.

Most patients with Alzheimer's disease and Alzheimer's Disease Related Dementias (ADRD) experience the gradual onset and progression of cognitive symptoms, leading to decline over years or decades. However, in a small subset of patients, symptoms begin rapidly, leading to dementia within one year and complete incapacitation within two years of symptom onset. A new study at Mayo Clinic aims to determine why patients with Alzheimer’s disease and ADRD develop this rapidly progressive dementia (RPD).

"The factors that give rise to extreme, rapidly progressive clinical traits are unknown," says Gregg Day, M.D., a neurologist and clinical researcher at Mayo Clinic in Florida. "These cases are challenging to treat in practice because there are many possible causes and diseases to consider, many tests that can be done and a clear need to coordinate evaluations rapidly."

Dr. Day will lead a team of researchers from Mayo Clinic in Florida and Rochester, Minnesota, to study the biology of RPD through a project funded by the National Institute on Aging of the National Institutes of Health (NIA/NIH).

Specifically, the research team and collaborators aim to:

• Determine the factors that make patients with Alzheimer's disease and ADRD susceptible to RPD.
• Study the contributions of amyloid and tau toxic proteins and vascular changes in the brain to rates of progression in patients with Alzheimer's disease and ADRD.
• Identify cellular pathways that contribute to rapid declines in patients with Alzheimer's disease and ADRD.

The researchers plan to collect clinical and genomic information from 120 diverse patients with rapid progressive Alzheimer's disease and ADRD over the next three years. Findings in patients with RPD, identified through Alzheimer's Disease Research Centers studies nationally, will be compared with data from participants with typical progressive Alzheimer's disease and ADRD enrolled in studies at the Alzheimer's Disease Research Center at Mayo Clinic.  

The team hopes to learn how factors such as age, sex, medical history, structural and social determinants of health, genetic variants and other brain changes may make some patients more susceptible to rapid decline. Findings will be validated through expansive protein analyses in cerebrospinal fluid from an independent group of patients with autopsy-confirmed rapid progressive Alzheimer's disease and ADRD. Results will be extended to identify biomarkers and disease-modifying targets that may improve diagnosis and treatment of patients with Alzheimer's disease and ADRD.

"This project represents a substantial investment from NIH to study patients with RPD," says Dr. Day. "We hope the results of our research will inform new approaches, diagnostic tests and treatment targets that will improve outcomes in patients with AD/ADRD. The ultimate goal is to slow down the pathologic progression of disease in these patients, independent of their rate of decline."

The research will combine Mayo Clinic's expertise in digital innovation and telemedicine to engage patients across the United States. This study will also leverage Mayo's Clinical Trials Beyond Walls program, which allows patients to complete some, if not all assessments from the comfort of their own homes or local community facilities. The decentralized clinical trials initiative is designed to remove barriers to clinical trial participation by providing digital solutions and remote services to reimagine the trial experience for all involved, including participants, investigators, study teams and clinical care providers. Decentralized research ― studies conducted outside the walls of traditional research facilities ― may use a wide range of technologies and services such as telehealth, remote monitoring, mobile phlebotomy, retail pharmacy and home healthcare.

Other Mayo Clinic researchers working on this project include:

• Christian Lachner, M.D.
• Neill Graff-Radford, M.D.
• Leonard Petrucelli, M.D., Ph.D.
• Tania Gendron, Ph.D.
• Manoj Jain, M.D.
• Owen Ross, Ph.D.
• Nilufer Ertekin-Taner, M.D., Ph.D.
• Dennis Dickson, Ph.D.
• Melissa Murray, Ph.D.
• Vijay Ramanan, M.D., Ph.D.
• David T. Jones, M.D.
• Prashanthi Vemuri, Ph.D.
• Alicia Algeciras-Schimnich, Ph.D.
• John R. Mills, Ph.D.
• Rickey Carter, Ph.D.
• Lauren Haydu, Ph.D.

The research will be made possible through NIH grant award number R01 AG089380.

Related:

Researchers identify new criteria to detect rapidly progressive dementia

Researchers find other diseases may mimic rare brain disorder linked to dementia

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The bloodstream is teeming with plasma proteins that can increase and decrease depending on what is happening in the body. As a result, these proteins can serve as valuable biomarkers for health.

Mayo Clinic researchers have found that a specific plasma protein, called IL-23R, increases with age. The finding reveals a connection between a cellular aging process, called senescence, and specific plasma proteins in the blood that increase with age and decrease in response to therapeutics targeting senescent cells. This new discovery is published in Nature Aging.

"Our research is the first to show that IL-23R is an aging biomarker linked to senescence. Since IL-23R influences many inflammatory conditions that can increase with age, our discovery opens new lines of investigation as to how circulating IL-23R may influence disease processes with age," says senior author Marissa Schafer, Ph.D.

IL-23R is known to alert immune cells to help fight infections through inflammation, the body's defense mechanism. However, when IL-23R is overactive, it can lead to tissue damage and drive the persistent inflammation that underlies conditions such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis.

The research team measured IL-23R levels in donated blood samples of 40 men and 40 women ranging in age from 20 to 90 years old. They found that IL-23R increased in blood circulation with age among the participants. Using a preclinical model, they showed that IL-23R is linked to markers of senescence in aged organs, particularly the kidneys.

Additionally, the researchers tested five different senotherapeutics, drugs specially designed to eliminate senescent cells. All of these drugs targeted genes or proteins that are highly expressed in senescent cells. They found the senotherapeutics reduced the amount of plasma proteins including IL-23R.

"By targeting and reducing senescent cells, we can influence the systemic landscape by decreasing inflammatory mediators that are secreted in tissues and into circulation, such as IL-23R. This suggests that IL-23R is an important aging biomarker in senescence, inflammation and organ 'cross talk' that may be useful in clinical research and practice," explains lead author Chase Carver, Ph.D.

Next steps and implications

The researchers are continuing to study how circulating IL-23R is produced, how it affects inflammatory signaling throughout the body and how it drives disease states.

They are also collaborating with others to assess if other senotherapeutic approaches or exercise reduce circulating IL-23R levels in humans.

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

The post Researchers discover an aging and inflammation biomarker appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — How long a person can stand — on one leg — is a more telltale measure of aging than changes in strength or gait, according to new Mayo Clinic research. The study appears today in the journal PLOS ONE.

Good balance, muscle strength and an efficient gait contribute to people's independence and well-being as they age. How these factors change, and at what rate, can help clinicians develop programs to ensure healthy aging. Individually, people can train their balance without special equipment and work on maintaining it over time.

In this study, 40 healthy, independent people over 50 underwent walking, balance, grip strength and knee strength tests. Half of the participants were under 65; the other half were 65 and older.

In the balance tests, participants stood on force plates in different situations: on both feet with eyes open, on both feet with eyes closed, on the non-dominant leg with eyes open, and on the dominant leg with eyes open. In the one-legged tests, participants could hold the leg they weren't standing on where they wanted. The tests were 30 seconds each.

Standing on one leg — specifically the nondominant leg — showed the highest rate of decline with age.

"Balance is an important measure because, in addition to muscle strength, it requires input from vision, the vestibular system and the somatosensory systems," says Kenton Kaufman, Ph.D., senior author of the study and director of the Motion Analysis Laboratory at Mayo Clinic. "Changes in balance are noteworthy. If you have poor balance, you're at risk of falling, whether or not you're moving. Falls are a severe health risk with serious consequences."

Unintentional falls are the leading cause of injuries among adults who are 65 and older. Most falls among older adults result from a loss of balance.

In the other tests:

• Researchers used a custom-made device to measure participants' grip. For the knee strength test, participants were in a seated position and instructed to extend their knee as forcefully as possible. Both the grip and knee strength tests were on the dominant side. Grip and knee strength showed significant declines by decade but not as much as balance. Grip strength decreased at a faster rate than knee strength, making it better at predicting aging than other strength measures.
• For the gait test, participants walked back and forth on an 8-meter, level walkway at their own pace and speed. Gait parameters didn't change with age. This was not a surprising result since participants were walking at their normal pace, not their maximum pace, Dr. Kaufman says.
• There were no age-related declines in the strength tests that were specific to sex. This indicates that participants' grip and knee strength declined at a similar rate. Researchers did not identify sex differences in the gait and balance tests, which suggests that male and female subjects were equally affected by age.

Dr. Kaufman says people can take steps to train their balance. For example, by standing on one leg, you can train yourself to coordinate your muscle and vestibular responses to maintain correct balance. If you can stand on one leg for 30 seconds, you are doing well, he says.

"If you don't use it, you lose it. If you use it, you maintain it," Dr. Kaufman says. "It's easy to do. It doesn't require special equipment, and you can do it every day."

Funding for this study includes the Robert and Arlene Kogod Professorship in Geriatric Medicine and W. Hall Wendel Jr. Musculoskeletal Professorship.

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Media contact:

• Rhoda Madson, Mayo Clinic Communications, newsbureau@mayo.edu

The post Mayo Clinic study: What standing on one leg can tell you appeared first on Mayo Clinic News Network.

The Mayo Clinic Brain Bank is home to more than 11,000 brain tissue samples used for research studies worldwide. About 3,000 of those donated brains come from patients across the state of Florida. Now, a new grant will help fund community outreach and computer technology programs that make it easier for researchers to access the brain bank and share discoveries in neurodegenerative diseases.  

The Alzheimer's Association Florida Gulf Coast Chapter has awarded the grant to Melissa Murray, Ph.D., a professor of neuroscience and co-director of the Mayo Clinic Brain Bank. Dr. Murray is also director of the Translational Neuropathology Laboratory at Mayo Clinic in Florida, which has a mission to prevent Alzheimer's disease and related dementias. The funds are designated to the Florida Autopsied Multi-Ethnic (FLAME) Cohort within the brain bank, which focuses on the diversity of abnormal proteins found in brains and seeks to ensure the inclusion of Hispanic and Black American brain donors. 

The risk of developing dementia is 1.5 times greater in Hispanic Americans and twice as high in Black Americans compared with non-Hispanic white Americans, according to Mayo Clinic researchers.

"Brain banking is built around a compassion for families and care partners to provide closure through diagnostic evaluation of the brain. The scientific goal of brain banks is to characterize, store and share tissue with qualified researchers to accelerate therapeutic discoveries by uncovering a deeper understanding of how disease affects these patients," says Dr. Murray.

"Brain banking is a costly endeavor that is difficult to obtain funding for and, with an ever-increasing demand for tissue sharing, we need to find ways to enhance workflow," she says. "This grant will help us develop technology that can be used to support documentation of important information critical for scientific discoveries. Perhaps even more importantly, this grant will fund efforts to share knowledge with, and learn from, Hispanic and Black communities affected by Alzheimer's disease and related dementias."

Specifically, the funding will support outreach and education efforts, as well as preliminary support for the development of a website that can connect with a database system for the brain bank. Erica Engelberg-Cook, Ph.D., the Mayo Clinic Brain Bank community and scientific liaison, will work with researchers to identify their research needs, which can be used to design an online system for tissue requests.

The Mayo Clinic Brain Bank was established in 1991 on the Mayo Clinic in Florida campus and led by Dennis Dickson, M.D., since 1998. The donated brains are shared with researchers at Mayo and academic medical centers around the world to advance studies on the pathology of diseases and conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Lewy body dementia, progressive supranuclear palsy and stroke.

The brain bank receives donations from across the nation through programs such as the Alzheimer's Disease Research Center and from across the state through the Florida Alzheimer's Disease Initiative.

The brains are obtained at autopsy after patients' consent and are sent to the brain bank for diagnostic evaluation and research studies. The brain bank also collects non-diseased brain tissue to establish control groups for studies.

"Through the sharing of human tissue, researchers at Mayo Clinic and around the world are one step closer to directly improving patient care," says Dr. Murray. "There is also a great need for people unaffected by disease to donate their brains to allow us to understand the aging process. Even more important is the need to enhance brain donations from underrepresented groups through the sharing of knowledge and learning from communities."

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Mayo Clinic researchers have found that senescent cells — non-dividing "zombie" cells — accumulate in the skin as people age and may influence aging in other parts of the body. Their recent study revealed that transplanting senescent skin cells into a preclinical model revealed that they not only caused that senescence to spread to other tissues but also accelerated physical decline, impaired muscle function and adversely affected brain health. This discovery indicates that senescent cells in the skin could drive broader, systemic aging.

"This discovery is significant because it suggests that senescent cells in the skin — an organ not typically associated with aging, beyond wrinkles — might be driving broader, systemic aging processes. These findings could also help explain the link between skin conditions and cognitive decline, offering potential new pathways for addressing both physical and mental deterioration as we age," says Mayo Clinic researcher João Passos, Ph.D., who is one of the lead authors on the study, published recently in Aging Cell.

This research also offers support for anti-aging strategies that aim to keep both the body and mind healthier for longer.

"This study suggests that skin senescence may accelerate aging in other organs, highlighting the importance of preventing factors like sun exposure, smoking, alcohol and poor diet that contribute to premature skin aging," says Ana Catarina Franco, the study's first author and Mayo Clinic visiting graduate student.

The researchers aim to investigate whether senolytic drugs, originally developed at Mayo Clinic and shown to eliminate senescent cells among people with a high number of senescent cells, can improve overall health when applied topically to the skin. They also plan to do more research to try to understand the mechanisms by which senescent cells may spread from the skin to other organs.

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

The post Could ‘zombie cells’ in the skin be aging your brain too? appeared first on Mayo Clinic News Network.