USF Health researchers are studying how a little-known protein known as BIN1 may contribute to the formation of tangles in the brain that are a hallmark of Alzheimer’s disease, a degenerative brain condition that affects more than 6 million Americans today.

Their findings have been published in the peer-reviewed Brain: A Journal of Neurology. Leading the study was Gopal Thinakaran, PhD, CEO of the USF Health Byrd Alzheimer’s Center and Research Institute and professor of molecular medicine in the USF Health Morsani College of Medicine. Contributing to the report were Moorthi Ponnusamy, PhD, and other members of the Thinakaran Lab at the Byrd Institute.

The paper focuses on a protein called Bridging Integrator 1 – or BIN1 – a protein that is found in cells in the brain and other organs. Understanding BIN1 has been a challenge because it appears in different forms in brain cells, but breakthroughs could lead to improved therapies for people who develop Alzheimer’s as they age.

“Aging is the leading risk factor for Alzheimer’s disease,’’ Dr. Thinakaran said. “A comparison of small changes in the DNA of people worldwide with and without Alzheimer’s disease found up to 40% carry small changes in the BIN1 gene, and many of those are at a higher risk for developing the disease.’’

Until recently, other proteins, such as beta amyloid and tau, which contribute to the formation of plaques and tangles in the brain, have received more attention from researchers. But now scientists are turning to risk factors such as BIN1, believing understanding their function might offer targets for potential treatments.

BIN1 is the second-most prevalent genetic risk factor identified for late-onset Alzheimer’s disease. It encodes an adaptor protein that regulates certain functions in the brain, and evidence suggests BIN1 can alter the dynamics of cell membranes within the brain.

Thinakaran’s team looked at whether the presence of BIN1 inside the brain’s neurons favors the accumulation of tau, a toxic protein, in structures called tangles. Greater numbers of these tangles in the brain have been associated with memory loss and the death of brain cells.

The team found that laboratory mice without BIN1 in their neurons developed only milder degeneration in the regions of the brain essential for memory. Also, brain inflammation was reduced by the loss of BIN1, suggesting that BIN1 in neurons also influences nerve, or glial, cell activation during the development of Alzheimer’s disease.

“These findings mean that BIN1 in neurons promotes Alzheimer’s disease tau pathology, stimulates brain inflammation, and contributes to memory loss, thus identifying BIN1 as a possible drug target,’’ Dr. Thinakaran said.

The timing of the team’s work is critical: The number of Americans affected is expected to rise to 13 million by 2050 and cost the United States more than $1 trillion, according to the Alzheimer’s Association, a global voluntary health organization dedicated to care, support and research.

Alzheimer’s is a specific brain disease that progressively and irreversibly destroys memory and thinking skills. Eventually, Alzheimer’s disease takes away the ability to carry out even the simplest tasks.

The vast majority of people who develop Alzheimer’s dementia are age 65 or older. Experts believe this late-onset Alzheimer’s, like other common chronic diseases, develops as a result of multiple factors rather than a single cause. Although a handful of laboratories worldwide are studying how BIN1 is involved in the disease process, Thinakaran’s team is leading the research efforts to define how BIN1 acts as a risk for Alzheimer’s disease in the elderly.

Their work is funded by three major research grants totaling $7 million from the National Institute on Aging, which is part of the National Institutes of Health, along with grants from the Cure Alzheimer’s Fund and the Alzheimer’s Association.

In June, the USF Health group published a related study in the journal Molecular Neurodegeneraton, which described BIN1’s impact on glial cells, which are responsible for brain inflammation.

— Story by Kurt Loft for USF Health News 

Seeking help at the first signs of Betty’s memory loss, the Boysens continue to live each day fully rather than letting the disease define them

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“Once the travel bug bites there is no known antidote.” This famous quote defines Al and Betty Boysen.

The couple, whose relationship spans more than 72 years, has traveled to every continent but Antarctica, including 49 states, leaving Hawaii off the list because as Betty says “it’s a lot like Florida.”

Dr. Amanda Smith (left), director of clinical research at the USF Health Byrd Alzheimer’s Institute, speaks with Al and Betty Boysen.

A few years ago, they sold their last motor home after Betty was diagnosed with Alzheimer’s disease. Just a mile and a half away from home, Betty began seeing Amanda Smith, MD, the director of clinical research at the USF Health Byrd Alzheimer’s Institute. The Byrd Institute — home to a highly-qualified team of researchers, doctors, clinicians and educators — is a state-of-the-art center at the forefront of Alzheimer’s research and care.

“Al and Betty sought help at the first sign something was wrong,” Dr. Smith said. “Because of that, we were able to intervene right away with medication and preserve some of her memory and daily function, which allowed them to continue to travel for longer than they might have otherwise.”

The Boysens have traveled to to every continent but Antarctica, including 49 of the 50 U.S. states.

A little lost in caring for his wife of seven decades, as her disease progressed, Al searched for help and found the center’s support group a comfort.

“We’ve enjoyed a combination of friendship and information sharing since I started taking advantage of the support group,” said 93-year-old Al, who also supports caregiver education at the Byrd Center through his philanthropy. “Caregivers go through a form of suffering, just like the patient, so the meetings help many of us in different ways.”

“The Boysen’s are making the most of every day,” Dr. Smith said. “They utilize all of the resources, so the disease becomes something that they’re living with rather than what defines them.”

Betty (first row, 9th from left) and Al (top row, 11th from left) met as Class of 1950 students at Cornell College, Mount Vernon, Iowa.

A medic and chaplain’s assistant in the U.S. Army during World War II, Al spent time caring for survivors at the Ebensee Concentration Camp in Austria shortly after the war ended.

When Al returned stateside, he enrolled at Cornell College in Iowa. There, he met the woman of his dreams, Betty Cain. Betty worked and lived at the president’s house to pay her way through college. When Al and Betty became engaged, the president’s wife, Arrola Bush Cole, planted a “Matrimonial Maple” tree on campus in their honor.

Al and Betty Boysen on their wedding day: April 2, 1950

The Boysens followed careers in education, with Betty adding an M.A. degree from USF in 1979. She developed a curriculum for special needs children and was named the program’s director when the state of Florida adopted the Florida Diagnostic and Learning System.

Without children of their own, they were foster parents to many. They were so dedicated to foster care that Betty was named the “Foster Mother of the Year” in the early 1960s in their then-hometown of Chicago.

“All through life, we enjoyed the same thing. The first from our families to attend college, we had a lot in common,” Al said.

The Boysens’ first motor home in 1957

Their summers off were spent wandering the globe. In 1986, when Betty retired, they sold their house, placed a few prized possessions in storage and gave the rest away to travel for five years. A few years later, they traveled another two years between owning homes.

Many times they traveled with a cat and christened their 12 different motor homes with clever names like “Big Red” and “Old Blue.”

“A lot of women would probably have hated it. I thought it was wonderful,” 89-year-old Betty said. “We’ve been everywhere and done everything — we think.”

One of the Boysens’ last motor homes

Their travel escapades helped them fill almost three dozen scrapbooks. “It would be hard to look through the books and pick my favorite memory, because we liked so many places and so many people,” Betty said.

They took trips with a South African couple they met on their travels. Once the two couples took a barge tour up and down three rivers in the U.S. “That was fun! We really enjoyed showing the Velthuizens what life was like in our country,” Betty said.

The Boysens continue to work with Dr. Smith to help them navigate this journey of Alzheimer’s.

Betty Boysen relaxes in the motor home with one of the family cats.

For a long time, people thought dementia was just a normal consequence of aging, Dr. Smith said.  “It’s a disease. We can slow it down, we can help preserve cognition and function over years. We can provide education and support for caregivers. We can treat behavior issues and some of the emotional things patients experience that go along with having this. There’s a lot that can be done; people just have to come in and seek help early.”

The Boysens are a shining example of how, by seeking help early, persons living with Alzheimer’s disease can continue to make the most out of life.

The Boysens look through old photo albums from their many trips.

Though the scrapbook pages continue to yellow with age, when Al and Betty sit down to flip through them, a single picture brings back a thousand memories. In the words of Japanese author Banana Yoshimoto, “Truly happy memories always live on, shining. Over time, one by one, they come back to life.”

Photo by Torie M. Doll

-Video by Torie M. Doll, USF Health Communications and Marketing

Tampa, FLA (Jan. 17, 2017) — The University of South Florida has launched a neurosciences initiative to integrate the latest treatment and research for a wide range of neurological and psychiatric disorders.

With the state-of-the-art USF Health Byrd Alzheimer’s Institute as its centerpiece and driving force, the new neuroscience initiative is being spearheaded by Dr. Harry van Loveren, vice dean of clinical affairs for the USF Health Morsani College of Medicine and chair of the Department of Neurosurgery and Brain Repair. Dr. van Loveren has a proven track record of highly effective administrative and clinical leadership skills, having served as interim dean of the USF medical school and developed one of its most successful departments. He is widely respected regionally and nationally as a top neurosurgeon and researcher with expertise in skull base surgery as well as microneurosurgical techniques.

Harry van Loveren, MD

The multidisciplinary initiative will bring together medical, surgical and research specialists from USF Health’s departments of neurology, neurosurgery and psychiatry – all dedicated to advancing treatment and prevention of brain, spinal cord and other nervous system disorders.

“The primary goal of this larger neurosciences initiative is to foster and coalesce interdisciplinary research collaboration among USF Health scientists looking at the brain in unique ways to accelerate new discoveries for a broad range of neurological conditions – including Alzheimer’s and related dementias, Parkinson’s, ataxias, epilepsy, multiple sclerosis and stroke – leading to improved treatment and prevention for the patients we serve,” said Dr. Charles Lockwood, senior vice president for USF Health and dean of the Morsani College of Medicine.

“Dr. van Loveren has the expertise and commitment to build a preeminent, strong neurosciences model that will provide an even greater infrastructure for moving neurological discoveries from bench to bedside,” Dr. Lockwood said.

By consolidating disease-specific areas of care for a wide spectrum of neurological conditions, the initiative is expected to strengthen collaborative, complementary research across USF neuroscience disciplines and allow patients to better access the care they need.

“We will build upon the success of the Byrd Alzheimer’s Institute in becoming a vital treatment and research center for Floridians affected by Alzheimer’s disease and other memory disorders,” Dr. van Loveren said.

“The neurosciences initiative will unify and coordinate all resources at the university for neurological and neuropsychiatric disorders so we can expand our neurosciences footprint and serve even more patients and their families. We envision USF Health becoming a national destination for all things related to brain disorders and brain health.

The endeavor will also help position USF to take advantage of new federal funding opportunities such as the National Institutes of Health’s BRAIN Initiative, a pioneering project aimed at revolutionizing the understanding of the brain and accelerating the development and application of new technologies for brain disorders.

                                                                                                                   -USF Health-
USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Physical Therapy and Rehabilitation Sciences, the Biomedical Sciences Graduate and Postdoctoral Programs, and the USF Physicians Group. USF Health is an integral part of the University of South Florida, a high-impact, global research university dedicated to student success. For more information, visit www.health.usf.edu

Media contact:  
Anne DeLotto Baier, USF Health Communications
(813) 974-3303 or abaier@health.usf.edu

USF Health neuroscientist Chad Dickey, PhD — a leading NIH-funded researcher in the Morsani College of Medicine who developed an international reputation seeking answers to some of the most fundamental questions about neurodegenerative disorders, particularly Alzheimer’s disease – died Nov. 25, after a courageous battle with cancer.  He was 40.

“Many of us were truly privileged to work with Dr. Dickey, who was a brilliant neuroscientist bursting with creativity and a passion for discovery and scientific collaboration,” said Charles J. Lockwood, senior vice president for USF Health and dean of the Morsani College of Medicine. “He accomplished more in a decade than most investigators achieve in far longer tenure.

“We honor the outstanding scientific legacy Chad has left for us to build upon. He will be greatly missed, and his memory will live on in his many discoveries.”

Dr. Dickey was an associate professor of molecular medicine and psychiatry and a research scientist at James A. Haley Veterans’ Hospital.

While his impact on the field of neurosciences reached worldwide, his roots were planted firmly at the University of South Florida.  A Tampa native, he obtained both his bachelor’s degree in microbiology and PhD in pharmacology and neuroscience from USF. After completing a postdoctoral fellowship in neuroscience from the Mayo Clinic in Jacksonville, he returned to USF as a faculty member in 2006.

Dr. Dickey’s early work was as a member of a team that determined a vaccine may be a useful approach to treating Alzheimer’s disease.  He was the first to find that proteins involved in learning and memory were selectively impaired in mouse models of Alzheimer’s.

Much of his recent NIH-supported work focused on defects in the removal of damaged proteins by cells. Dr. Dickey’s promising studies of the key role “chaperone proteins” play in brain cell function were originally directed at Alzheimer’s disease, but subsequently expanded to other disorders ranging from glaucoma to depression to preterm birth. He wanted to find drugs to reverse defects leading to the buildup of harmful substances in the brain known as “tau tangles,” which are linked to the progression of Alzheimer’s disease — and he made considerable progress in that quest.

Dr. Dickey worked with Dave Morgan, PhD, for all but two of the last 17 years.

“He was a PhD student, research associate and research assistant professor in our laboratory. And for the last seven years he was a star faculty member in the Byrd Alzheimer’s Institute and Department of Molecular Medicine,” said Dr. Morgan, Distinguished USF Health Professor and CEO of the USF Health Byrd Alzheimer’s Institute.  “Thus, his loss is especially personal to me.”

Over his academic career, Dr. Dickey received 20 grants totaling more than $15 million from the NIH, Alzheimer’s Association and other organizations and published 65 scientific papers cited more than 4,000 times by other researchers.

“Equally important, Chad has trained an impressive group of PhD students and postdoctoral fellows, many of whom have gone on to successful biomedical research careers and will carry on his legacy,” said Robert Deschenes, PhD, professor and chair of the Department of Molecular Medicine.

Many colleagues and students have expressed an outpouring of sympathy and sadness upon learning of Dr. Dickey’s passing.

Edwin Weeber, PhD, a professor of molecular pharmacology and physiology and chief scientific officer at the Byrd Alzheimer’s Institute, admired his friend and colleague’s unflagging collaborative approach as a lead investigator.

“What I remember most about Chad was his constant smile, morning, noon and night. He was always in a pleasant mood, and his door was open to everyone,” Dr. Weeber said.  “Regardless of whether he was under the pressure of a grant deadline or preparing for a lecture, he always made time for you, even if it was just to chat.  Beyond his scientific acumen, he found a way to successfully balance the rigors of being a friend and colleague, a husband and father, and a scientist.”

Former doctoral student John O’Leary said Dr. Dickey helped him grow into a professional when he entered his lab at age 23 — supporting him through difficult times, and accepting his ultimate decision to leave academic science to become a jazz musician.

“He taught me how to work hard, and what it meant to have drive and passion. Once I was having a bad day and decided to escape the lab for a bit, and Chad found me eating a six pack of donuts in my black Yaris, in the parking lot of the Byrd at 11 am; I was so embarrassed. Although, he didn’t say anything, he didn’t have to. I knew his expectations for me were high,” O’Leary said.

“He pushed me to go beyond my comfort zone and continually challenged me in my learning as a scientist, a speaker, a thinker, a doer,” O’Leary said. “However, he was equally goofy as he was intense. One of my favorite memories is of him rapping Coolio’s “Gangsters Paradise” while doing bench work.”

Jose Abisambra, PhD, a former postdoctoral scholar in Dr. Dickey’s laboratory, now an assistant professor at the University of Kentucky Sanders-Brown Center on Aging, said that as a mentor Dr. Dickey led by example.

“During late nights, we would sometimes find him in his office writing a grant. Despite being so young, Dr. Dickey offered wise advice from overcoming challenges in the lab and in life; I learned how to successfully balance a family and an exceptional career,” Dr. Abisambra said.

“After completing my postdoctoral training in his lab, I founded my own research group, and our success is based on the tenants of impeccable work ethic, creativity, collaboration, and gratefulness, which I learned from him… He profoundly impacted my life as a scientist and as a person. I am certain that all of us who were fortunate to have trained with Chad will strive to carry out his legacy both in and out of the lab.”

Visitation will take place 10 a.m., Friday, Dec. 2, followed by a memorial service at 11 am, all at Idlewild Baptist Church in Lutz.  In lieu of flowers, donations can be made to the Dickey Education Fund to aid in the future education costs of Chad and his wife Adria’s two sons. For more information, please visit: https://www.youcaring.com/adrialukeandjakedickey-701981

For the obituary and guest book, click here.

Photos by Eric Younghans, USF Health Communications

Older adults who completed 11 or more sessions of training had a 48 percent reduced risk of dementia over the 10-year study period, a University of South Florida researcher finds

 TAMPA, Fla. (July 25, 2016) – A particular type of brain training can significantly and substantially reduce risk for dementia, said University of South Florida (USF) associate professor Jerri Edwards, PhD, in a presentation made yesterday in Toronto, Canada, at the Alzheimer’s Association International Conference.

“This is the first time a cognitive intervention has been shown to protect against dementia in a large, randomized, controlled trial,” said Dr. Edwards, a faculty member in the USF School of Aging Studies and an associate member of the USF Health Byrd Alzheimer’s Institute. “Relatively small amounts of training resulted in up to a 48 percent decrease in the risk of dementia over the 10-year study period.”

Dr. Edwards reported on the latest results from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study, a 10-year study on cognition and aging funded by the National Institute on Aging.

Jerri Edwards, PhD, an associate professor at the USF School of Aging Studies and associate member of the USF Health Byrd Alzheimer’s Institute, studies cognitive performance, including how quickly the brain can process information and act on it.

The ACTIVE Study enrolled 2,802 healthy older adults at six sites around the United States, and randomized the participants into four groups: 1) an intervention group receiving 10 one-hour sessions of classroom instruction on memory strategies; 2) an intervention group receiving the same amount of instruction on reasoning strategies; 3) an intervention group receiving the same amount of computerized brain training, involving perceptual practice and; 4) a control group measured at the same times as the intervention groups.

All participants were assessed on a number of cognitive and functional measures at the completion of the initial 10 sessions of training (after five weeks) and at follow-up visits at years one, two, three, five and 10. Subsets of each intervention group also received four additional “booster” training sessions at years one and three. In releasing the current results, the researchers looked at the risk of developing dementia over the 10-year period across all four groups.

Researchers found no significant difference in risk of dementia for the strategy-based memory or reasoning training groups as compared to the control group. However, as compared to the control group, the computerized brain training group were 33 less likely to develop dementia across 10 years, a statistically significant difference (p=0.012).

The researchers further saw a significant dose-response function. After adjusting for other variables indicating risk for dementia (e.g., race, sex, mental status, physical status, depressive symptoms), participants who engaged in 11 or more sessions of the computerized brain training showed a 48 percent reduction risk of dementia as compared to the control group (p=.005).

Participants in the computerized brain training group were trained on a highly specific task designed to improve the speed and accuracy of visual attention, including both divided and selective attention exercises. To perform the divided attention training task, a user identifies an object at the center (i.e., car or truck) of gaze while at the same time locating a target in the periphery (i.e., car). As the user gets the answers correct, the speed of presentation becomes progressively briefer, while the targets become more similar. In the more difficult training tasks, the target in the periphery is obscured by distracting objects, engaging selective attention.

A brain training exercise like that found on BrainHQ.com pushes a user to progressively improve visual speed of processing, with attentional demands both at the center of gaze and periphery.

There is substantial prior scientific literature on this training exercise, which is referred to as “speed of processing training”, “useful field of view training”, or “UFOV training.” The exercise was developed by Dr. Karlene Ball of the University of Alabama Birmingham and Dr. Dan Roenker of Western Kentucky University. It is now exclusively licensed to Posit Science Corporation, and is available as the “Double Decision” exercise of the BrainHQ.com brain training program.

Dr. Edwards noted that this particular training regimen has previously been shown effective in multiple clinical trials and, unlike other approaches, has been found to improve the everyday functional abilities of older adults. “These new data”, she said, “further demonstrate the longitudinal benefit of reducing risk of dementia.”

The benefits of the program are believed to be driven by engaging brain plasticity in a way that improves attention and up-regulates the chemical (neuromodulatory) system.

“We need to further delineate what makes some computerized cognitive training effective, while other types are not,” Dr. Edwards said. “We also need to investigate what is the appropriate amount of training to get the best results, Given that 10 to 14 sessions had these benefits, what would the effects of larger doses be? “

“Clearly, the time spent on effective brain training has potential long-lasting benefits for many aspects of older adults’ lives,” she concluded.

                                                                                           ###

The University of South Florida is a high-impact, global research university dedicated to student success. USF is a Top 50 research university among both public and private institutions nationwide in total research expenditures, according to the National Science Foundation. Serving nearly 48,000 students, the USF System has an annual budget of $1.5 billion and an annual economic impact of $4.4 billion. USF is a member of the American Athletic Conference.

Media contact:
Shani Fails, M.A., Director, Communications & Marketing
USF Health Byrd Alzheimer’s Institute
sfails@health.usf.edu or 813-396-0675

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The USF Health Byrd Alzheimer’s Institute unveiled its mobile Memory Research Suite on June 28 – a groundbreaking traveling “clinic” designed to bring the latest clinical drug trials to senior communities across Florida.

That makes the institute the first academic research facility in the state with a mobile clinical trials unit dedicated to finding new treatments for Alzheimer’s disease, a memory-robbing illness that affects more than 5 million Americans and this week claimed the life of legendary women’s college basketball coach Pat Summit.

USF Health Byrd Alzheimer’s Institute leaders cut the ribbon inaugurating the institute’s new mobile Memory Research Suite.

Although current drugs help mask the symptoms of Alzheimer’s disease, there are not yet effective medications to treat the underlying disease or to significantly delay its progression.

David Morgan, PhD, CEO of the Byrd Alzheimer’s Institute, says that 15 investigational drugs for Alzheimer’s disease and other forms of dementia are in the last stage (Phase 3) of clinical study with more in the pipeline, but getting promising drugs to the Food and Drug Administration for review can take four to five years, including more than two years for full enrollment of patients in a trial.

“We need to get drugs to patients sooner,” Dr. Morgan said. “We’re trying to accelerate the entire process, and we think that ideas like this will help do that and increase opportunities for drug study participation for a much broader range of Floridians than exists today.”

Bill and Sheila Nagley were among the guests to tour the mobile clinical trials suite. They currently drive monthly from south St. Petersburg to the Byrd Institute in Tampa, where Bill participates in an Alzheimer’s drug clinical trial.

Scheduled to begin operation in August, the Memory Research Suite features a reception area, patient exam room, two testing rooms, an Americans with Disability Act compliant restroom, a phlebotomy area for blood draws as well as central air conditioning and wireless Internet access. The Byrd Institute’s clinical experts staffing the mobile unit will evaluate study participants and administer investigational medications at pre-selected study sites, expected to include memory disorder clinics, outpatient medical clinics, hospitals, churches, retirement communities.

“Up to this point, we were limited to only being able to enroll people willing to travel to our site,” said Amanda Smith, MD, medical director of the Byrd Alzheimer’s Institute. “By bringing a fully-functioning mobile unit to them, we hope to increase enrollment in trials, increase diversity in research, decrease the time it takes to complete the studies and, ultimately shorten the time it takes to get new treatments to the market.”

Ed Funai, MD, chief operating officer of USF Health and vice president of strategic development for USF said: “Today is a defining moment that positions USF Health as a national leader in addressing Alzheimer’s and other memory-related disorders.”

Ed Funai, MD, chief operating officer for USF Health and vice president of strategic development for USF, thanked the Byrd Institute faculty and staff for all they do to help position USF Health as a national leader in the fight against Alzheimer’s disease.

“We all know someone who has been affected by this horrible disease,” Dr. Funai said. “Clinical trials are essential for the development of more effective and efficient prevention, diagnoses and treatments for Alzheimer’s and memory-related disorders… What will take place inside our new mobile Memory Research Suite will make life better for generations to come.”

USF mascot “Rocky” the Bull with David Morgan, PhD, CEO of the Byrd Alzheimer’s Institute.

Following a ribbon-cutting, guests and media toured the 400-square-foot clinical research space on wheels, which was designed in collaboration with industry leaders from research organizations.

Among the guests was Sheila Nagley and her husband Bill, 74, who was diagnosed with Alzheimer’s disease in 2009. They make the more than one hour drive from their home in south St. Petersburg to the Byrd Institute monthly so that Bill can participate in an Eli Lilly-sponsored Phase 3 clinical trial testing whether solanezumab, a monoclonal antibody designed to help reduce build-up of amyloid plaques in the brains of people with early stages of Alzheimer’s, can slow the disease’s progression.

Amanda Smith, MD, medical director of the USF Health Byrd Alzheimer’s Institute

Bill does not know if the IV infusion he receives is the investigational drug or not; half of the participants in the double-blind randomized controlled study receive solanezumab and the other half get a placebo. But, at the end of the 18-month trial all participants are eligible for the medication.

“We don’t mind the drive (to Tampa), but if this portable facility was available closer to us in our community, we’d choose to use it,” Sheila said. “We started coming to the Byrd Institute in 2012, and they’ve really improved our quality of life with all their resources, including a support group and clinical trials. Having access to people actually doing the research is great.”

The mobile unit was specifically designed make cutting-edge clinical research studies in Alzheimer’s disease more accessible to elderly Floridians and their families across the state.

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Video by Sandra C. Roa, and photos by Eric Younghans, USF Health Communications and Marketing

New dementia drug discovery efforts get underway this month at the University of South Florida, Tampa, Fla., thanks to £875,000 funding (approximately $1.2 million) from the Dementia Consortium. The U.S. team of academics will work with drug development experts at UK-based MRC Technology, to target the immune system in a bid to halt nerve cell damage.

The investment comes as part of the £4 million Dementia Consortium – a global partnership between Alzheimer’s Research UK, MRC Technology and the pharmaceutical companies Abbvie, Astex, Eisai and Lilly. By uniting expertise, the Consortium is bridging the gap between academic research and the pharmaceutical industry in the search for new drugs to slow neurodegenerative diseases.  The Consortium’s project with the University of South Florida marks their first contract for collaboration with an American University.

The link between the immune system and neurodegeneration is the focus of intense investigation, and a number of drug discovery efforts aimed at reducing inflammation have got underway recently. In this collaborative project, Dr. David Morgan and Dr. Kevin Nash of the USF Health Byrd Alzheimer’s Institute, University of South Florida, will explore the role of immune system regulator, fractalkine, in neurodegeneration. Their previous work in animal models of Alzheimer’s disease indicated a neuroprotective role for the protein, with increased levels of fractalkine dampening inflammation, halting nerve cell death and reducing tau deposits. The team observed similar benefits in mouse models of Parkinson’s, suggesting that fractalkine receptor agonism could be a treatment approach for a number of neurodegenerative diseases.

David Morgan, PhD, CEO of the USF Health Byrd Alzheimer’s Institute and Distinguished University Health Professor (left) and Kevin Nash, PhD, assistant professor of molecular pharmacology and physiology, with an image of neurons expressing fractalkine, an immune system regulator with a neuroprotective effect.

As no known small molecule agonists of the fractalkine receptor exist, the Dementia Consortium funding will couple Dr Morgan’s expertise in neurodegeneration and in vivo validation techniques with the MRC Technology’s extensive screening capabilities and medicinal chemistry programmes.

Talking about the new funding, Dr. David Morgan, CEO of the USF Health Byrd Alzheimer’s Institute, said:

“We’ve been exploring the role of fractalkine in Alzheimer’s and Parkinson’s disease for many years now, highlighting a neuroprotective role for the protein. Thanks to funding from the Dementia Consortium, we are now able to shift our focus from pathway characterization to drug development. We’re particularly excited that this approach could have an impact across a number of different neurodegenerative diseases and look forward to coupling our disease knowledge with drug discovery experts in the UK, to help accelerate progress towards treatments.”

Dr. Simon Ridley, Director of Research at Alzheimer’s Research UK, said:

“Dementia is our greatest medical challenge, with 46 million people worldwide living with the condition. The Dementia Consortium is one of a range of initiatives by Alzheimer’s Research UK to accelerate the ‘bench to bedside’ journey, ensuring that academic insights are translated into the clinic as rapidly as possible. The high attrition rate in drug discovery means we must invest heavily in promising early stage development projects and the Dementia Consortium provides a unique vehicle for this investment, uniting expertise across the academic, technology transfer and pharmaceutical sectors.”

Close-up of microscopic image: magnified neurons expressing fractalkine.

Dr. Justin Bryans, Director, Drug Discovery at MRC Technology, said:

“Scientists are increasingly looking at the body’s own immune system to fight some of the most challenging diseases of our time. This project will progress promising findings that fractalkine could reduce inflammation and cell death. Drug discovery expertise in our laboratories will now be applied to find small molecules to stimulate the fractalkine receptor so we can move a step closer to finding a new treatment for people with dementia.”

On forming new partnerships, Valerie McDevitt, Associate Vice President for Technology Transfer & Business Partnerships at the University of South Florida, said:

“The University of South Florida places emphasis on building new relationships like this one to help bridge the gap between academic research and industry.  Our collaboration with the Dementia Consortium provides an opportunity to positively impact the treatment of neurodegenerative diseases and aligns with our university mission to serve as a highly effective major economic engine.”

# # #

For further information, or to speak with Dr. Morgan or Dr. Ridley, please contact Emma O’Brien, Science Communications Officer at Alzheimer’s Research UK on 0300 111 5 666, mobile or email press@alzheimersresearchuk.org.

USF Health PhD graduate Justin Trotter leaves this weekend for Stanford University School of Medicine in Palo Alto, CA, where he will work for a recent Nobel Prize winner in medicine.  Trotter’s postdoctoral fellowship will play out in the large laboratory of Stanford neuroscience researcher Thomas Sudhof, MD, a Howard Hughes Medical Institute investigator who just last week jointly won the 2013 Nobel Prize in Physiology or Medicine for insights into the traffic control system for living cells.

Justin Trotter, PhD, (left) USF Health neuroscience graduate, with major professor Edwin Weeber, PhD, chief scientific officer of the USF Health Byrd Alzheimer’s Institute.

“That just doesn’t happen very often,” said Edwin Weeber, PhD, professor of molecular pharmacology and physiology and chief scientific officer of the USF Health Byrd Alzheimer’s Institute.   Dr. Weeber was Trotter’s major professor while the young neuroscientist completed his doctoral studies in neuroscience at the Byrd Institute.

“Justin is the most driven graduate student I’ve had the pleasure to mentor,” Dr. Weeber said. “His ability to gain a fellowship with a Nobel Prize winner in one of the country’s top laboratories shows that USF and the Byrd Institute are training the next generation of scientists whose research will make a real difference.”

Trotter successfully defended his doctoral dissertation “Cellular and Molecular Mechanisms of Reelin Signaling in the Adult Hippocampus” on Sept. 27.  His doctoral research focused on signaling pathways important in brain development and their role in molecular mechanisms that give rise to learning and memory and that may be disrupted by Alzheimer’s disease.

“When I spoke to Tom (Sudhof) to endorse Justin’s application to his laboratory, I told him that Justin was the most brilliant young scientist I had ever met,” said Joachim Herz, MD, of the Department of Molecular Genetics, University of Texas Southwestern Medical Center, who served as the external chair for Trotter’s dissertation committee.

“My only concern and advice to Tom was that he should cut his travels short in the future, otherwise he might find Justin running the laboratory upon his return.”

2013 Nobel Prize-winning neuroscience researcher Thomas Sudof, MD

Probing the neurobiology of learning and memory

For a person to think, move, feel or remember, the neurons in that person’s brain must communicate across junctions known as synapses. Increasing evidence has linked impairments in synaptic transmission to diseases such as Alzheimer’s and autism.

Working with Dr. Sudhof’s team, Trotter will still study how nerve cells communicate with one another to precisely exchange information across synapses within millisecond timescales. But at Stanford he will focus on the role of signaling pathways in autism instead of Alzheimer’s.

Trotter was offered postdoctoral fellowships at three of the country’s leading research institutions — the National Institutes of Health Eunice Kennedy Schriver National Institute of Child Health and Human Development, the Gladstone Institute affiliated with the University of California San Francisco, and, his first choice, Stanford University

He interviewed with Dr. Sudhof and 15 of his postdoctoral fellows July 19 and was offered the position by Dr. Sudhof  himself a week later, well before the Nobel Prize announcement.

“When I saw that he was on a team that made the finalists, I thought wouldn’t it be fun if he actually won,” Trotter said. “Then, the awards committee made the announcement the next day, and people were congratulating me – but I didn’t really do anything.”

Early fascination with science cultivated on a fish farm

Trotter grew up in Palm Bay, FL, but spent most weekends working on a tropical fish farm in nearby Fellsmere, where his father and grandfather operated the acquaculture business. He attributes his early fascination with science to what he learned on the fish farm, including how to breed and care for African cichlids.

In elementary school, while many classmates relied on their parents for help with science fair projects, Trotter looked forward to the challenge of creating and carrying out his own experiments.

“Science projects became my means of self-expression,” said Trotter, who won many regional and state science fair awards throughout middle and high school.  “I enjoyed designing experiments to test assumptions and garner facts about the natural world.”

By 10^th grade he worked his way into an independent research project at Florida Institute of Technology, where he studied the molecular biology of starfish fertilization.  During one late-night experiment, Trotter said, he accidently hit his hand on a glass pipette filled with mercury. A hospital X-ray showed the shattered glass (from the broken pipette) scattered around a joint where the mercury injected.

“After about a week my hand was swollen and I had to get it operated on,” he said. “To this day I still have a small black, metallic circle near the injection site… Fortunately the type and quantity of mercury I was exposed to poses no danger.”

By 11^th grade Trotter was testing algae extracts from the Indian River Lagoon and the Antarctica for anti-cancer properties.  He even set up a temporary lab culture room at his house when the laboratory space where he worked was taken over by scientists preparing experiments to accompany a Columbia space shuttle flight.

“I needed to determine whether the extracts that I had prepared possessed the ability to slow down the division rate of leukemia cells,” he said. “Needless to say, my mom learned to avoid wondering what I was doing in the den.”

Passion for neuroscience nurtured at USF

Trotter has spent the last five years at USF, where he says his passion for neuroscience was nurtured. He earned a bachelor of science degree in biomedical sciences here, followed by a master’s of science and PhD degrees in medical sciences, both with a concentration in neuroscience.

Along the way he has co-authored 15 journal articles with Dr. Weeber and/or other USF faculty members, including Lynn Martin, PhD, of the Department of Integrative Biology.  He was a member of an interdisciplinary team awarded a highly competitive 2012-13 USF Graduate Student Research Challenge Grant.  Dr. Weeber and Trotter also have a patent pending for a new therapeutic approach for treating brain injuries.

At the USF Health Byrd Alzheimer’s Institute, Trotter found in Dr. Weeber a mentor who shared his passion for delving into how synapses work with the hope that the research will lead to future treatments for Alzheimer’s disease or other cognitive disorders.

“I’ve really enjoyed the collaborative spirit at the Byrd Institute,” Trotter said.  “They’ve provided me with the resources and support needed to move forward in the development of my scientific career.”

And this USF graduate continues to move ahead — taking his place next month in the laboratory of a new Nobel Prize winner.  “It’s an amazing opportunity,” Trotter said.

– Photos by Eric Younghans, USF Health Communications

Tampa, FL (Oct. 1, 2013) — The USF Health Byrd Alzheimer’s Institute will hold Alzheimer’s & the Arts, an evening of artistic expression, 6 to 9 p.m., Saturday, Nov.  23, at the Institute, 4001 E Fletcher Ave, Tampa, FL 33613.  The fundraiser will benefit research, patient care and education.

The inaugural event will feature live entertainment and an online auction.  Performers include accomplished jazz pianist and singer Lillette Jenkins-Wisner of Orlando. The 89-year-old former Sarasota resident, who was diagnosed with memory loss at the Byrd Institute, will perform with her daughter and granddaughter. Other performers include the Shoes At the Door Dance Company comprised mostly of graduates from USF’s School of Theatre and Dance, vocalist and Byrd Institute CEO Dave Morgan, PhD, and the La Lucha jazz band featuring Alzheimer’s researcher John O’Leary on piano.

An important part of the fundraiser will be an online auction beginning Nov. 9 and concluding at the event. The auction will include original artwork created by people living with Alzheimer’s and donated by the families of residents at Arden Courts memory care facilities (Tampa, Sarasota and Seminole).  Guests can also bid on a variety of items donated by community partners such as SeaWorld/Aquatica, Tradewinds Resorts, and Charles Jewelers, to name a few.

Guests can bid on auction items displayed at the event from any location using their smartphones or designated on-site computers.  They will also have the opportunity to “Make their Mark against Alzheimer’s” with a fun interactive activity.

The event includes hors d’oeuvres, beer and wine.  Registration is $100 per person. To make a reservation, please visit: http://health.usf.edu/byrd/alzandartsevent.htm.

The online auction will begin at 8 a.m. Saturday, Nov.  9, and run through Nov. 23 at 8:30 p.m.  Bidding will be available through Bidding for Good online and/or mobile smart phones before and during the event. To access online auction, visit www.biddingforgood.com/byrdinstitute.

For more information, contact Holly Lisle at (813) 974-0890 or hlisle@health.usf.edu.

 -USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities.

USF-led study suggests FKBP51 is a new treatment target for diseases with tau pathology

Tampa, FL (Sept. 3, 2013) — A stress-related protein genetically linked to depression, anxiety and other psychiatric disorders contributes to the acceleration of Alzheimer’s disease, a new study led by researchers at the University of South Florida has found.

The study is published online today in the Journal of Clinical Investigation.

Dr. Chad Dickey of the USF Health Byrd Alzheimer’s Institute was principal investigator for the study.

When the stress-related protein FKBP51 partners with another protein known as Hsp90, this formidable chaperone protein complex prevents the clearance from the brain of the toxic tau protein associated with Alzheimer’s disease.

Under normal circumstances, tau helps make up the skeleton of our brain cells.  The USF study was done using test tube experiments, mice genetically engineered to produce abnormal tau protein like that accumulated in the brains of people with Alzheimer’s disease, and post-mortem human Alzheimer’s brain tissue.

The researchers report that FKBP51 levels increase with age in the brain, and then the stress-related protein partners with Hsp90 to make tau more deadly to the brain cells involved in memory formation.

Hsp90 is a chaperone protein, which supervises the activity of tau inside nerve cells. Chaperone proteins typically help ensure that tau proteins are properly folded to maintain the healthy structure of nerve cells.

However, as FKBP51 levels rise with age, they usurp Hsp90’s beneficial effect to promote tau toxicity.

“We found that FKB51 commandeers Hsp90 to create an environment that prevents the removal of tau and makes it more toxic,” said the study’s principal investigator Chad Dickey, PhD, associate professor of molecular medicine at the USF Health Byrd Alzheimer’s Institute. “Basically, it uses Hsp90 to produce and preserve the bad tau.”

The researchers conclude that developing drugs or other ways to reduce FKB51 or block its interaction with Hsp90 may be highly effective in treating the tau pathology featured in Alzheimer’s disease, Parkinson’s disease dementia and several other disorders associated with memory loss.

A previous study by Dr. Dickey and colleagues found that a lack of FKBP51 in old mice improved resilience to depressive behavior.

The latest study was supported by a grant from the National Institute of Neurological Disorders and Stroke.

Article citation:
“Accelerated neurodegeneration through chaperone-mediated oligomerization of tau;” Laura J. Blair, Bryce A. Nordhues, Shannon E. Hill, K. Matthew Scaglione, John C. O’Leary III, Sarah N. Fontaine, Leonid Breydo, Bo Zhang, Pengfei Li, Li Wang, Carl Cotman, Henry L. Paulson, Martin Muschol, Vladimir N. Uversky, Torsten Klengel, Elisabeth B. Binder, Rakez Kayed, Todd E. Golde, Nicole Berchtold, and Chad A. Dickey; Journal of Clinical Investigation, Vol. 123, No. 10. DOI:10.1172/JCI69003.

Watch a video of Dr. Dickey explaining the role of chaperone proteins in regulating tau:

//www.youtube.com/watch?v=AuBBVreGX-k

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-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities.

Media contact:
Anne DeLotto Baier, USF Health Communications
(813) 974-3303, or abaier@health.usf.edu