Research by Laura Blair’s team seeking to untangle tau may lead to targeted treatments for Alzheimer’s, Parkinson’s and other neurodegenerative diseases

Both of USF Health neuroscientist Laura Blair’s grandmothers died from ALS, a debilitating neurodenerative disease that progressively weakens muscles and leads to paralysis.

Laura Blair, PhD, assistant professor in the Department of Molecular Medicine, at her laboratory in the USF Health Byrd Alzheimer’s Institute

“Seeing that firsthand really put in my heart to do everything I could to help people suffering from these devastating neurodegenerative diseases,” said Blair, PhD, an assistant professor in the Morsani College of Medicine’s Department of Molecular Medicine.

As an USF undergraduate student conducting research in chemist Bill Baker’s laboratory, she had the chance to work at the USF Health Byrd Alzheimer’s Institute with Chad Dickey, PhD, an accomplished and creative NIH-funded neuroscientist who was the first to find that proteins involved in learning and memory were selectively impaired in a mouse model of Alzheimer’s disease.

Blair jumped at the opportunity.  Dr. Dickey’s National Institutes of Health (NIH) work was focusing on defects in the removal of damaged proteins from cells, with promising studies of the key role “chaperone proteins” play in regulating brain cell function in Alzheimer’s disease and other neurodegenerative disorders.

“I was excited to be part of the translational work he was doing – seeking to understand how the cell’s natural defense, these chaperone proteins, might be harnessed to regulate (abnormal) misfolding proteins in order to help fix or prevent neurodegenerative disease,” Dr. Blair said.

That was nine years ago.

Dr. Blair pulls up microscopic images of stained neurons with doctoral student Lindsey Shelton, right. The stain is used to determine if treatments administered to mice —  for instance, overexpressing cochaperone protein Aha1 or human enzyme CyP40 — change how toxic tau becomes to nerve cells.  

 Dr. Laura Blair describes the focus of her laboratory’s research.

Carrying on a scientific legacy

Since then, Dr. Blair received her doctorate in medical sciences at USF in 2014 (she also earned bachelor’s and master’s degrees here) and continued to work in Dr. Dickey’s laboratory as a postdoctoral fellow.  When Dr. Dickey passed away last year at the age 40 following a courageous battle with cancer, Dr. Blair and colleague John Koren, PhD, assumed the leadership of Dickey’s team with heavy hearts. But they push forward with their mentor’s same dedication to seeking answers and sense of urgency to “publish, publish, publish.”

“Chad was always larger than life and one of the biggest influences in my life, so losing him has been surreal,” said Blair, who keeps Dr. Dickey’s nameplate on the office she now occupies. “It’s hard, but we will continue the work he started and carry on his scientific legacy.”

“He was a tremendous mentor who taught all of us how to think about a problem and ways to come up with solutions.” And she said, smiling at the memory of Dr. Dickey’s unrelenting drive to find solutions, “he taught us there’s no sense in waiting until tomorrow for an experiment that could have been started yesterday.”

Dr. Blair with Jeremy Baker, doctoral candidate in the Department of Molecular Medicine who was the lead author for a recent PLOS Biology paper reporting that a human enzyme can reduce neurotoxic amyloids in a mouse model of dementia.

Dr. Blair’s laboratory studies how chaperone proteins drive different states of the tau protein associated with Alzheimer’s disease and more than a dozen other tauopathies, including Parkinson’s disease and traumatic brain injury.  Just as their name suggests, “chaperone” proteins escort other proteins in the cell to the places they need to be, ensure these proteins do not interact with others that could be bad influences, and see to it that proteins degrade, “or are put to bed, so to speak,” when the time is right, Dr. Blair said. Under normal circumstances, chaperone proteins help ensure tau proteins are properly folded to maintain the healthy structure of nerve cells.

Pursuing how chaperones drive different states of tau

In particular, the USF researchers explore how various chaperone proteins interact, for better or worse, with various forms of tau – ranging from soluble tau protein that can spread from one brain cell to another to the aggregated, misfolded species of tau tangles inside brain cells.  (Sticky plaques of B-amyloid protein and toxic tangles of tau protein both accumulate in patients with Alzheimer’s disease, but recent studies suggest that tau deposits may be more closely linked to the actual death of neurons leading to memory loss and dementia.)

“If we can understand which states of tau are worse in terms of driving neurotoxicity,” Dr. Blair said, “maybe we can begin to shift tau into a better state so we can help delay disease progression, if not stop it in its tracks.”

 Dr. Blair comments on differences in Alzheimer’s disease.

Dr. Blair and colleague John Koren, PhD, assistant professor (far left), co-manage a research team focusing on how chaperone proteins drive different states of the tau protein associated with Alzheimer’s disease and more than a dozen other tauopathies.

.With a support of a new five-year, $1.5-million R01 grant from the National Institute on Aging, Dr. Blair, along with co-principal investigators Paula Bickford, PhD, of the USF Center of Excellence for Aging and Brain Repair, and Vladimir Urvesky of the Department of Molecular Medicine, is looking at a family of energy-independent, small heat shock proteins known to prevent harmful tau aggregation.  In an earlier paper published several years ago in the Journal of Neuroscience, Drs. Blair, Dickey and colleagues reported that high levels of one of these chaperone proteins, Hsp27, reduced tau accumulation in neurons and rescued learning and memory in a mouse model for Alzheimer’s disease.

Dr. Blair is also principal investigator of a second, five-year $1.36-million grant from the National Institute of Mental Health (the continuation of a grant originally awarded to Dr. Dickey) to develop a treatment blocking the effect of a stress-related protein genetically linked to depression, anxiety and other behaviors associated with post-traumatic stress disorder (PTSD). The grant builds upon earlier USF research, showing that as levels of this stress-related protein, known as FKBP51, increase in the brain with age it partners with chaperone protein Hsp90 to make tau more deadly to brain cells involved in memory formation. Using a new mouse model genetically engineered to overexpress FKBP51 and exhibit symptoms like those seen in humans with PTSD, Dr. Blair’s team will test various treatments on mice exposed to early-life environmental stresses.

Dr. Blair and Shelton, lead author of a USF-led paper published this September in Proceedings of the National Academy of Sciences demonstrating that Hsp90 cochaperone Aha1 boosted production of toxic tau aggregates in a mouse model of neurodegenerative disease. 

The ultimate goal of all this tau regulation research is to discover and commercialize targeted treatments that work, whether that’s drugs that inhibit or activate chaperone proteins, or gene therapies, or a combination. Currently no FDA-approved medications for Alzheimer’s disease specifically target beta amyloid or tau; they only help improve symptoms for some patients for a limited time.

A single-bullet therapeutic approach to a disease like Alzheimer’s that affects diffuse areas of the brain is unlikely, Dr. Blair said. “The multi-treatment option is probably going to be the most effective, but it’s difficult to address that until we have individual treatments moving forward.”

“Working toward treatments to help slow and prevent these devastating neurodegenerative diseases is what keeps our laboratory so motivated and determined.”

 On working in a building that bridges research and clinical care

Slides, containing stained nerve cells from mouse brain tissue, are used by the researchers to evaluate neuronal health following various treatments.

Identifying potential treatments for neurodegenerative diseases

Building on Dr. Dickey’s work with chaperone proteins, the USF researchers continue to make significant progress in identifying potential targets to help slow or prevent neurodegenerative disease progression.

The team recently identified cochaperone protein Aha1, which binds to and stimulates the activity of heat shock protein Hsp90, as one promising therapeutic target.  Hsp90 regulates the folding, degradation and accumulation of tau. In a study published this September in  Proceedings of the National Academy of Sciences, the researchers demonstrated that Hsp90 cochaperone Aha1 boosted production of toxic tau aggregates in a mouse model of neurodegenerative disease and led to neuron loss and memory impairment.

The researchers also found that inhibiting Aha1 prevented the dramatic accumulation of tau in cultured cells. “We think Aha1 inhibitors offer promise for effects similar to Hsp90 inhibitors with less side effects,” Dr. Blair said.

Dr. Blair and Shelton work at an automated stereotactic injector station. The equipment helps the researchers determine the effects of gene therapy in the brain.

This June, in the journal PLoS Biology, Dr. Blair (principal investigator), Jeremy Baker (lead author) and colleagues reported for the first time that a naturally-occurring human enzyme – called cyclophilin 40 or CyP40 – could break apart clumps of tau in a mouse model of dementia. The USF led study found that CyP40 reduced the amount of aggregated tau, converting it into a more soluble and less toxic form of amyloid. In a mouse model of an Alzheimer’s-like disease, experimental expression of CyP40 preserved brain neurons and rescued cognitive deficits. The same enzyme also disaggregated alpha-synuclein, an aggregate associated with Parkinson’s disease.

Exactly how CyP40 can untangle clumps of tau and alpha-synuclein is not yet clear, but, Blair said “our finding suggests that CyP40, or one of the more than 40 other proteins with similar activity, may have a role to play in treating neurodegenerative diseases.”

Dr. Blair points to the hippocampus on the map of a mouse brain. An area critical for learning and memory, the hippocampus is especially vulnerable to damage at early stages of Alzheimer’s disease.

 What Dr. Blair hopes she can impart to students as a mentor

Some things you might not know about Dr. Blair:

• Blair and her husband Tom belong to a local swing dancing community, where they enjoy dancing the Lindy Hop and Balboa to ‘40s jazz.
• Blair is a mother to 7-year-old Oliver, and a stepmother to 17-year-old Laney, who is a high school senior. They also have two dogs, a Shih Tzu named Oreo and a Shih Tzu-Yorkshire terrier mix named Pumpkin.
• Participating in the Great American Teach-in two years ago, Dr. Blair spoke to her son’s kindergarten class about her career as a neuroscientist, including working on brain teaser puzzles and discussing a video of a preclinical neurobehavioral test with the young students. But, she said, the kids were particularly impressed with the squishy plastic “stress-reliever brains” she brought along.

Research associate Leo Breydo loads protein into a gel.

Cultured cells are harvested for analysis.

-Photos by Sandra C. Roa and Eric Younghans, University Communications and Marketing

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two rare neurodegenerative diseases also considered as spectrum disorders, affect thousands of Americans every year.

ALS, a condition that effects nerves and muscles, and FTD, a disorder that causes changes in behavior and personality, language, motor skills and function, are associated with one another due to a common genetic mutation in multiple genes.

David Kang, PhD, professor of molecular medicine, in his laboratory at the USF Health Byrd Alzheimer’s Institute. He was the study’s lead author. 

However, researchers did not know exactly why that happened until a new research breakthrough at University of South Florida Health in Tampa, Florida.

A group of USF Health researchers found that a mutated ALS and FTD gene is pathologically linked to mitochondria dysfunction and TDP-43 pathology – causing problems for people affected by either disease.

The results of this study were published in Nature Communications Journal.

The study’s lead investigator David Kang, PhD, professor of molecular medicine and researcher at the USF Health Byrd Alzheimer’s Institute, said that this is a very important pathological link for ALS and FTD.

“Mutations in the ALS and FTD gene, called CHCHD10, are instigating dysfunction in the mitochondria, the cell powerhouse plants that produce the majority of the energy in the human body,” Dr. Kang said. “This gene allows TDP-43, a protein that’s part of the nuclear function, to exit the nucleus to get into the cytoplasm or cell body and cause TDP 43-pathology – which is relatively specific to ALS and FTD.”

While many genes cause ALS and FTD, this gene is the first one that’s been linked to mitochondria, Dr. Kang said. Dr. Kang and his team of researchers have worked on this study for two years, supported by grants from the Veterans Administration, National Institutes of Health and Florida Department of Health.

Dr. Kang (second from right) with some members of his research team. From left: JungA (Alexa) Woo, PhD, assistant professor; Courtney Trotter, graduate research assistant; and Tian Lu, PhD, postdoctoral research scholar, Department of Molecular Medicine, USF Health Morsani College of Medicine.

To come up with the results, the USF Health researchers studied worms, mammalian cell lines, primary neurons and mouse brains. The models allowed them to prove that the mutated gene is very important to the mitochondrial function, which the human body needs.

“We took the human gene, CHCHD10, and we put it into worms with a short life-span,” Dr. Kang said. “We used worms who lacked the CHCHD10 gene and had dysfunctional mitochondria, which, as a result, had motor problems and could not move properly. What happened was that the normal human gene helped the worms live longer – completely rescuing their abnormalities and restoring their mitochondria function and movement. However, when we put the single mutated gene that causes ALS and FTD into the worm, it did not rescue at all. They were still completely dysfunctional.”

The USF Health research team suggests that these results are critical to ALS and FTD research. This was the first study to show that the normal gene increases mitochondria function and the mutant gene increases mitochondria dysfunction. The normal gene is bound to TDP-43 protein and allows it to stay in the nucleus.

Alexa Woo, PhD

However, when TDP-43 pathology is outside the nucleus, it decreases mitochondria function and synaptic integrity, connecting points between neurons. Researchers said synapse loss occurs in all neurodegenerative diseases.

This is an important step into the right direction, but researchers at USF Health agree that there is more work to be done.

“I think ultimately, if we can understand how the neurodegenerative disease leads to aberrations at the molecular level, then we can potentially target specific molecules that induce pathology in ALS or FTD,” Dr. Kang said.

Photos by V.  Hysenlika

The Byrd Alzheimer’s Institute is participating in a nationwide study looking at whether Medicare should cover the costly amyloid PET scan

TAMPA, FL (July 24, 2017) — Amyloid build-up in the brain is a crucial component of Alzheimer’s disease. A brain amyloid PET scan can detect the sticky plaque, signaling its severity. But most patients can’t afford it as the scan costs as much as $11,000 out of pocket.

The USF Health Byrd Alzheimer’s Institute is participating in the nationwide “Imaging Dementia-Evidence for Amyloid Scanning” (IDEAS) study. Researchers are investigating the significance of the amyloid-detecting PET scan to help determine if it should be covered by Medicare. That conclusion will be drawn by comparing the patient’s initial management plan to the one created based on data from the amyloid PET scan.

Dr. Amanda Smith leads clinical research in Alzheimer’s disease at USF Health.

Of the 4,000 IDEAS participants who’ve so far completed their 90-day follow-up, about 70 percent have had their management plans altered. This includes drug therapy, counseling and additional testing. The Byrd Alzheimer’s Institute reports having similar results in its 23 patients enrolled so far.

“Amyloid PET scanning has really revolutionized our ability to accurately diagnose Alzheimer’s disease,” said Amanda Smith, MD, medical director of the USF Health Byrd Alzheimer’s Institute. “Our hope is that by demonstrating how these scans impact doctors’ decision-making, we can show how they save insurance dollars in the long run, and have them become part of the standard medical workup for dementia.”

Byrd Alzheimer’s Institute is enrolling additional participants who are existing patients. IDEAS intends to enroll 18,000 Medicare beneficiaries with mild cognitive impairment. The study is intended to prove early diagnosis will provide patients more accurate drug treatment plans and reduce unnecessary hospitalizations. 

 *Preliminary results were presented at the 2017 Alzheimer’s Association International Conference in London.

The USF-led study suggests CyP40 or similar proteins may be potential therapeutics for Alzheimer’s and Parkinson’s diseases

TAMPA, Fla. (June 27, 2017) — A naturally occurring human enzyme –called cyclophilin 40 or CyP40– can unravel protein aggregates that contribute to both Alzheimer’s disease and Parkinson’s disease, reports a study led by researchers at the University of South Florida in Tampa and published today in the open access journal PLOS Biology. The finding may point toward a new therapeutic strategy for these diseases.

This is the first time that CyP40 has been shown to disaggregate, or dissolve, a toxic, soluble form of amyloid responsible for a neurodegenerative disease, according to Laura Blair, PhD, an assistant professor in the Department of Molecular Medicine at the USF Health Byrd Alzheimer’s Institute.  Blair and fellow USF researchers worked with colleagues from several institutions in Germany.

USF neuroscientist Laura Blair, PhD, principal investigator for the study, in her laboratory at the USF Health Byrd Alzheimer’s Institute.

The study found that CyP40 could reduce the amount of aggregated tau, converting it into a more soluble and less toxic form. In a mouse model of an Alzheimer’s-like disease, experimental expression of CyP40 preserved brain neurons and rescued cognitive deficits. The same enzyme also disaggregated alpha-synuclein, an aggregate associated with Parkinson’s disease.

In most neurodegenerative diseases, misfolded proteins accumulate abnormally to form an insoluble clump called amyloid. Many amyloid-forming proteins, including tau in Alzheimer’s disease and α-synuclein in Parkinson’s disease, contain the amino acid proline, which has a unique structure inducing a bend in the amino acid chain. Those bends contribute to stacking of adjacent regions of the protein promoting clumping. CyP40 may dissolve these insoluble clumps by interacting with prolines within the amyloid structure.

Exactly how CyP40 reduces aggregation is not yet clear, and the authors provide two possibilities. The enzyme may bind to aggregated protein and, by reversing the proline bend, help unstack and separate the amino acid chain. Support for this model comes from the observation that the enzyme was less effective at reducing aggregates when its action was inhibited. Alternatively, the enzyme may bind to the protein before it forms aggregates, sequestering it and thus preventing the potentially harmful clumping.

Dr. Blair with Jeremy Baker, a doctoral candidate in the Department of Molecular Medicine and a lead author on the PLOS Biology paper. Pictured on the monitor are tau oligomers.

Understanding more specifically how the enzyme works may help point toward a therapeutic strategy centered on proline’s role in amyloid formation.

“The finding that Cyp40 can untangle clumps of tau and alpha-synuclein suggests that it, or one of the more than 40 other human proteins with similar activity, may have a role to play in treating neurodegenerative disease,” Blair said.

The study was supported by grants from the National Institutes of Health, the Alzheimer’s Association and the Veterans Health Administration.

Citation:
Human cyclophilin 40 unravels neurotoxic amyloids; Jeremy D. Baker, Lindsey B. Shelton, Dali Zheng, Filippo Favretto, Bryce A. Nordhues, April Darling, Leia E. Sullivan, Zheying Sun1, Parth K. Solanki, Mackenzie D. Martin, Amirthaa Suntharalingam, Jonathan J. Sabbagh, Stefan Becker, Eckhard Mandelkow, Vladimir N. Uversky, Markus Zweckstetter, Chad A. Dickey, John Koren III, and Laura J. Blair; PLOS Biology; June 27, 2017; https://doi.org/10.1371/journal.pbio.2001336

– Photos by Eric Younghans, USF Health Communications and Marketing

Researchers will focus on tau pathology in a mouse model to elucidate underlying causes.

Delirium is a serious form of mental impairment affecting 11 to 42 percent of elderly inpatients, particularly those hospitalized with infections, admitted to intensive care, or requiring surgery. The condition, marked by sudden-onset confusion and incoherence, is often underdiagnosed and can lead to devastating long-term health consequences.

Now, researchers at the University of South Florida have been awarded a five-year, $3.48 million grant from the National Institute on Aging (NIA) to investigate the observation that older adults who experience delirium while hospitalized can have higher risk afterwards of developing dementia.  They will also attempt to explain why the condition accelerates decline in patients who already have dementia.

The award titled “Influence of systemic immune inflammation upon the tauopathy phenotype in mouse models” will focus on tao pathology in a mouse model. Tau is one of the proteins that accumulates in Alzheimer’s brain tissue and is thought to cause the death of neurons. The grant was in response to a specific request from NIA for proposals forged by interdisciplinary investigative teams to address this question.

“The ultimate goal of this project is to identify the factors associated with general illness that impact Alzheimer’s pathology in the brain and block the influence of those factors on tau pathology, thus decreasing the risk or progression of dementia in individuals who develop general illnesses.” said principal investigator David Morgan, PhD, CEO of the USF Health Byrd Alzheimer’s Institute.

Dr. David Morgan.

“It is testimony to the breadth of expertise at USF that we were able to assemble this team of experts to tackle this very complex problem and compete successfully with other universities.”

Joining Dr. Morgan on the study are co-investigators from the USF Health Morsani College of Medicine and the USF College of Pharmacy: Paula Bickford, PhD, professor at the USF Center of Excellence for Aging and Brain Repair; Chuanhai Cao, PhD, associate professor of pharmaceutical science; Marcia Gordon, PhD, professor of molecular pharmacology and physiology; Daniel Lee, PhD, assistant professor of pharmaceutical science; Kevin Nash, PhD, assistant professor of molecular pharmacology and physiology; Maj-Linda Selenica, PhD, assistant professor of pharmaceutical science; and Ken Ugen, PhD, professor of molecular medicine.

This investigative team combines expertise in Alzheimer’s disease, aging brain function, innate immunity and adaptive immunology to unravel the mechanisms by which general illness can increase risk and progression of dementia.

The researchers suspect that hospitalization and immune activation may feed back onto the brain to speed up Alzheimer’s pathology, Dr. Morgan said. “However, like all epidemiology, it could be reverse causality.  That is, those with existing Alzheimer’s pathology may be more prone to delirium with major infectious illness.  The studies we do in mice will help determine what the direction is.”

Breathing, talking walking, remembering…. All these functions are coordinated by thousands of proteins out on the front lines keeping cells alive, healthy and working normally.  They are helped by molecules called chaperones that play a supervisory role in ensuring proteins are folded into their correct shapes. When something goes awry with the chaperones and proteins are misfolded, the good proteins may turn bad.

In his laboratory at the USF Health Byrd Alzheimer’s Institute, Chad Dickey, PhD, associate professor of molecular medicine and psychiatry and a research scientist at James A. Haley Veterans’ Hospital, leads a team studying chaperone proteins. The aim is to find ways to target these industrious assistants to treat neurodegenerative diseases known as tauopathies.  Abnormal accumulation of tau, a hallmark of protein associated with Alzheimer’s disease, is a feature of more than a dozen other disorders associated with loss of memory and movement, including progressive supranuclear palsy and Parkinson’s disease dementia.

USF Health Morsani College of Medicine neuroscientist Chad Dickey, PhD, with monitor displaying neurons.

The USF lab and others have begun to show that many diseases, inflammatory and cardiovascular as well as neurological, are in some way influenced by chaperones.

Last year, Dr. Dickey received two new R01 grants from the National Institutes of Health to help further USF’s chaperone protein research.

The first award — a five-year $1.95 million grant from the National Institute of Mental Health — will investigate how upregulation of the protein FKBP51 coordinates the brain’s response to stress.   Previous research by Dr. Dickey, published in The Journal of Clinical Investigation, showed that the age-related rise in levels of the stress protein FKBP51 usurps the beneficial effect of the stress-related protein’s chaperone partner Hsp90, thereby creating an environment that promotes tau toxicity and speeds the progression of Alzheimer’s disease.

The second award – a four-year, $1.74 million grant from the National Eye Institute – will be used to validate and improve upon a new specific inhibitor of the chaperone Grp94.  The Grp94 inhibitor, developed by Dr. Dickey’s team, accelerates the clearance of the genetically defective-protein myocilin known to cause the eye disease glaucoma.  Previous studies by the USF researchers, published in The Journal of Biological Chemistry and Human Molecular Genetics, found that Grp94 can interfere with the removal of the myocilin from cells and suggested that the chaperone offers a new target to treat some hereditary cases of glaucoma, a leading cause of blindness.

“There are still many unanswered questions about how chaperones work and fit into the protein-folding puzzle,” Dr. Dickey said. “But they certainly represent a lot of potential targets, and it’s our goal for USF to lead drug development efforts in the chaperone field for neurodegenerative diseases.”

Dr. Dickey and his team in one of their laboratories at the USF Health Byrd Alzheimer’s Institute.

Dr. Dickey joined USF Health as a faculty member in 2006 from the Mayo Clinic in Jacksonville, where he was an assistant professor of neuroscience.  He completed his post-doctoral training at Mayo under the direction of Dr. Michael Hutton, an expert in the field of Alzheimer’s disease genetics. He received his PhD in neuroscience from USF in 2004.

Dr. Dickey has authored or co-authored papers in more than 75 peer-reviewed journals, serves on the editorial board of Biochemical Journal and several other journals, and is a standing member of the NIH’s Drug Discovery for the Nervous System study section. He is a scientific advisory board member of the American Federation for Aging Research (AFAR) new investigator in Alzheimer’s disease program.

Photos by Eric Younghans, USF Health Communications

June 2, 2014 — USF Health will benefit from the University of South Florida System’s landmark support from state leaders, following Gov. Rick Scott’s signing today of the 2014-15 state budget.

Among the funding support that will advance USF Health initiatives:

–         One of the USF System’s top five legislative priorities this session, the USF Health Heart Institute had $15 million  allocated toward its construction cost.   This $15 million is combined with the nearly $20 million received for the Heart Institute during the previous two legislative sessions.

–         $5 million to be used towards the construction of a new state-of-the-art USF Health Morsani College of Medicine to replace the existing, outdated facility that was constructed in the early 1970s.

–         The USF Health Byrd Alzheimer’s Institute received $1.25 million in support.

–         Renewed funding renewed funding for the Bitner/Plante Amyotrophic Lateral Sclerosis Initiative of Florida,  providing $1 million to comprehensive ALS clinics across the state, including the USF Health ALS Center.

–       $500,00 in recurring funds for the USF Center for Neuromusculoskeletal Research based at the School of Physical Therapy & Rehabilitation Sciences.

Read the full news release about USF’s successful legislative session.

RELATED STORY:
Funding continues for comprehensive ALS care across Florida

Aging affects the risk of developing Alzheimer’s, heart disease, diabetes, cancer and other degenerative diseases as much as genetics and the environment, USF Health Byrd Alzheimer’s Institute CEO David Morgan, PhD, said in his testimony earlier this week before U.S. senators.

Dr. Morgan joined some of the nation’s leading experts on aging, who addressed the U.S. Senate Special Committee on Aging, Oct. 29 in Washington, DC, at a hearing about the value of research in tackling diseases of aging.

David Morgan (right), CEO of the USF Health Byrd Alzheimer’s Institute, speaks with Sen. Bill Nelson of Florida and Sen. Elizabeth Warren of Massachusetts, during a Senate Aging Committee roundtable with experts from across the country. Nelson chairs the committee.

Dr. Morgan’s opening statement included the following remarks:

“… The primary effect of aging is to decrease our ability to tolerate insults without having overt symptoms. As a result, a young person with, for example Alzheimer’s dementia, tends to have more severe changes in the brain than an old person does with Alzheimer’s dementia. The reason is the young person could compensate for small amounts of pathology, hence would not show symptoms of dementia unless the pathology was severe. Older persons have lost this ability to compensate, and even small amounts of pathology push them “over the edge” to a state of dementia.

One intriguing observation is that the lifestyle decisions that influence our risk of cardiovascular disease; exercise, diet, obesity, smoking; are the same factors that can influence our risks of dementia, cancer and diabetes. I suspect that these are not directly modifying the immediate causes of each disease, but are instead modulating the aging process, increasing our risk for whichever disorder we have the greatest genetic predispositions towards.”

In addition to leading the Byrd Alzheimer’s Institute, Dr. Morgan is a distinguished professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine; a lead representative for ResearchersAgainstAlzheimer’s,  and a member of the Florida Alzheimer’s Disease Advisory Committee.

The director of the National Institutes of Health’s National Institute on Aging yesterday visited the USF Health Byrd Alzheimer’s Institute, the state’s only freestanding Alzheimer’s center offering clinical assessment, laboratory research, education and care under one roof.

NIA Director Richard Hodes, MD, introduced by U.S. Rep. Kathy Castor and Byrd Alzheimer’s Institute CEO David Morgan, PhD, spoke about the NIA’s initiatives to build momentum in the fight against Alzheimer’s disease.   He also met with NIA-funded researchers from across USF and toured the Byrd Institute’s Center for Memory CARE.

Dr. Richard Hodes (left), director of the National Institute on Aging, and Dr. David Morgan, CEO of the USF Health Byrd Alzheimer’s Institute, listen as a faculty member explains his research project.

The NIA supports biomedical, clinical, behavioral, and social research related to the aging process, healthy aging, and age-related diseases and disabilities.  It is the primary federal agency funding and conducting Alzheimer’s disease research.

NIA-funded research at USF is approximately $3.5 million yearly, and  60 percent of the Byrd Alzheimer’s Institute funding is from NIA, Dr. Morgan said.

While working to understand the basic mechanisms of normal and abnormal aging, and to discover new treatments, prevention, and a cure for Alzheimer’s disease, Dr. Hodes said, the NIA also has a responsibility speed the translation of existing knowledge into practical therapies and public information.  The NIA also funds research to improve the quality of life for patients with Alzheimer’s disease and their caregivers.

Dr. Hodes outlined research advances since the first genes linked to an increased risk of Alzheimer’s disease were identified in the early 1990s.  These have included the development of mice genetically modified to exhibit the brain pathology of Alzheimer’s disease, genome-wide studies driving an integrated systems approach to find genes and networks that distinguish a brain affected by Alzheimer’s disease, and the identification of biomarkers to help with earlier detection and track disease progression.

L to R: Dr. Amanda Smith, medical director of the USF Health Byrd Alzheimer’s Institute, Institute CEO Dr. David Morgan: NIA Director Dr. Richard Hodes; U.S. Rep Kathy Castor, Institute Chief Scientific Officer Dr. Edwin Weeber, and Institute Associate Director Dr. Jessica Banko.

Most recently, revolutionary advances in imaging have allowed researchers to visualize nerve-killing Alzheimer’s amyloid proteins in the brain years before symptoms such as memory loss first appear. This innovative technology “gives us the ability to do clinical studies we could not do in the past,” Dr. Hodes said.

For example, he cited a new NIA randomized controlled clinical trial that will involve people at high risk for early-onset Alzheimer’s disease and test whether an immune therapy helps prevent amyloid accumulation or facilitates its clearance from the brain in these genetically-predisposed individuals.   Using imaging technology, investigators will track amyloid lesions in the brains of study participants who receive the investigational amyloid antibody and those who don’t.

“Over time they can see whether the treatment makes a difference or not,” Dr. Hodes said. “The goal is to find a way to intervene (early) before irreparable damage is done to the brain.”

Institute team members, including Director of Education Eileen Poiley (far left), led Dr. Hodes on a tour of the Center for Memory CARE.  Here they pause at the family room/kitchen area designed for the comfort and convenience of patients and caregivers.

Another emerging area of study for NIA is looking at how genes may interact with the environmental and behavioral factors to influence age-related cognitive decline.

Following his formal talk, Dr. Hodes met with about 20 USF faculty members supported by the NIA to learn more about their areas of study.   Their work includes such research as investigating the link between hearing and cognition; evaluating electrophysiological biomarkers for early-onset cognitive decline; testing nutritional approaches, like blueberries and spirulina, for protection against neural cell degeneration; searching for drugs or gene therapy to manipulate the chaperone proteins that regulate the fate of a hallmark Alzheimer protein known as tau; examining the role that the protein reelin plays in regulating and changing nerve cell connections in the region of the brain where new memories are formed; exploring cell-based therapies for Alzheimer’s disease; and using visual and auditory cues to help people with dementia remember better.

USF President Judy Genshaft greets Dr. Hodes.

Dr. Hodes was impressed by breadth and strength of  USF’s interdisciplinary aging research and recognized the distinctiveness of the Byrd Institute’s Center for Memory CARE, a one-stop multispecialty memory care center especially designed for Alzheimer’s patients and caregivers, Dr. Morgan said.  USF President Judy Genshaft and Stephen Klasko, MD, outgoing senior vice president of USF Health and medical school dean, accompanied Dr. Hodes on his tour of the facility.

USF faculty members whose research is supported by NIA met with Dr. Hodes to share the scope of their work.

Dr. Marcia Gordon (left), professor of molecular pharmacology and physiology, and Dr. Meredeth Rowe, professor of nursing, are among the NIA-supported faculty members at USF.

Dr. Hodes gets a look at the control room for the Institute’s onsite CT/PET scanner, which helps diagnose dementia and support drug discovery.

Dr. Hodes chats with Dr. Stephen Klasko, outgoing senior vice president of USF Health and medical school dean.

Dr. Hodes, a leading immunologist, has directed the National Institute on Aging since 1993 and devoted his tenure to developing a strong, diverse and balanced research program.

 Photos by Eric Younghans, USF Health Communications

Tampa, FL (Nov. 9, 2012) — The USF Health Byrd Alzheimer’s Institute has been awarded the Kendal Charitable Funds’ first Promising Innovations grant to develop an Alzheimer’s disease screening program that can be adapted for use in minority communities nationwide.

 The $25,000 grant will allow the Byrd Alzheimer’s Institute to bring an innovative, community-based approach to providing screenings for Alzheimer’s and other diseases causing memory loss to East Tampa, FL, an underserved, predominantly African-American community. Older African-Americans are about twice as likely as older whites to develop Alzheimer’s disease and other forms of dementia, according to the Alzheimer’s Association.

The Institute will collaborate with the National Black Nurses Association, Tampa Bay Chapter, to conduct the memory screenings, offer education about risk factors and explain screening results. Although there is no cure for Alzheimer’s disease, early diagnosis allows patients to enjoy a higher quality of life because current treatments can slow progression of the disease.

“We are fortunate to have a partnership with the Black Nurses Association of Tampa Bay to provide free memory screenings to East Tampa residents, and that the Kendal Corporation recognizes the value of providing this service to underserved communities,” said Jessica Banko, associate director of the USF Health Byrd Alzheimer’s Institute.

A panel of experts on aging selected USF’s proposal for funding from among more than 450 grant applications submitted to Kendal Charitable Funds from across the nation for model projects to improve services for older adults.  Projects that fit this broad purpose are in keeping with Kendal’s Values and Practices.

“By providing this grant, an underserved group with dementia will get help from nursing professionals — this is an innovative approach to a very substantial issue in an aging population,” says Bruce Stewart, chair of Kendal Charitable Funds. “Besides being innovative, this project also has the potential to be replicated to serve minority communities across America.”

“Kendal’s pursuit of better ways to address the unmet needs of older adults, coupled with the generosity of Kendal residents, board members, staff and others outside Kendal, led to the creation of the Promising Innovations grant program,” said Cheryl Wade, executive director for Kendal Charitable Funds. “Promising Innovations grants provide an outreach opportunity that allows us to collaborate with others outside the Kendal System in developing new ways to improve the quality of life and care for all older people.”

-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.

– Kendal Charitable Funds –

Kendal Charitable Funds was established in 1989 to raise and disburse funds in support of the charitable purposes of Kendal and its affiliates, including many outreach efforts. Those served by Kendal organizations and their boards and staffs, together with the wider constituency, support various funds for resident and member financial assistance, reaching out into the wider world, increasing the diversity of those served, and improving the experience of aging far beyond Kendal retirement communities and services. For more information contact: Larry Elveru, (610) 335-1232 or 484-623-6203, lelveru@kcorp.kendal.org

Media contact:
Shani Jefferson, Communications & Marketing, USF Health Byrd Alzheimer’s Institute
(813) 396-0675 or sjeffers1@health.usf.edu