Caring for a loved one with dementia can be overwhelming and isolating. Never was that more true than during the COVID-19 pandemic.

Eileen Poiley understands that challenge well, having dedicated more than 35 years to educating caregivers at the USF Health Byrd Alzheimer’s Center. When the world stopped, she knew this important work could not.

Poiley launched the Alzheimer’s Caregivers Podcast in May 2021 to offer practical guidance to caregivers where and when they need it. As the show posts its 100^th episode this month, this resource has helped more than 7,000 unique listeners around the world with downloads from six continents.

Eileen Poiley.

“Some caregivers are at the end of their ropes, and they don’t know what to do,” Poiley said. “We help caregivers deal with the challenges from a non-medication perspective, as there are a lot of behaviors that medication can’t change.”

The podcast features 30-minute episodes on a wide range of topics affecting families dealing with Alzheimer’s disease and dementia, including understanding short-term memory loss, managing the challenges of daily life, reducing safety risks, frequently asked questions and more.

Podcast producer Scott Huetteman, whose mother has Alzheimer’s disease, encouraged Eileen to create the podcast after hearing one of her presentations in person.

“There are a lot of ways to get information out, and the challenge with caregivers is that there is so much they need to know,” Huetteman said. “The podcast is a great way caregivers can listen to episodes any time of the day or night at their convenience.”

Poiley agrees that caregivers need a large volume of information, but that comprehensive books that cover a wide range of topics aren’t typically useful for caregivers. The podcast format allows them to pick the topic they need at the right moment.

Eileen Poiley.

One caregiver who has listened to all 100 episodes—several many times—said he was in a dire situation looking for help as he cared for his family member. She was diagnosed with Alzheimer’s five years before he reached out for support beyond medical care.

“I wish that I could reconstruct the morning I discovered the Institute,” said the caregiver, who asked to remain anonymous. “I had been looking through articles I had collected in a file over the previous five years, as her needs were getting well past what I could provide. Things were getting really emotionally intense for both of us.”

The Pinellas County caregiver became hopeful upon discovering the nearby virtual Alzheimer’s support programs at USF, along with the podcast series, through a Google search.

“It was like Eileen was here in the home, how she described what we were going through at the time,” said the caregiver. “She was spot on, and I could implement what I was learning and see almost immediate results.”

“My loved one and I are now both much calmer, in a better place, all because I listened to the podcasts. Eileen identified behaviors to watch for, explained them, and gave me strategies for how to respond and how to cope.”

Alzheimer’s disease is the 7^th leading cause of death in the United States, and one in three seniors dies with dementia.

To support Alzheimer’s caregiver education at USF Health, give online at usf.to/caregivers or contact Dan Minor at danielminor@usf.edu.

Story by Davina Gould, USF Foundation.

Preclinical study by a University of South Florida Health-University of Chicago research team offers new insights into how neuronal protein BIN1 may boost Alzheimer’s disease risk

TAMPA, Fla (March 11, 2020) — Bridging integrator 1, known as BIN1, is the second most common risk factor for late-onset Alzheimer’s disease, according to genome-wide studies of genetic variants. Yet, scientists know little about what this protein does in the brain.

Now a new preclinical study has discovered that a lack of BIN1 leads to a defect in the transmission of neurotransmitters that activate the brain cell communication allowing us to think, remember and behave. Led by Gopal Thinakaran, PhD, of the University of South Florida Health (USF Health) Morsani College of Medicine and colleagues at the University of Chicago, the study was published March 10 in Cell Reports.

USF Health’s Gopal Thinakaran, PhD, leads one of the few groups around the country studying BIN1 as a risk factor for late-onset Alzheimer’s disease. | Photo by Freddie Coleman

Approximately 40% of people with Alzheimer’s disease have one of three variations in the BIN1 gene – a glitch in a single DNA building block (nucleotide) that heightens their risk for the neurodegenerative disease, said the paper’s senior author Dr. Thinakaran, a professor of molecular medicine at the USF Health Byrd Alzheimer’s Center and associate dean for neuroscience research at the Morsani College of Medicine.

“Our findings that BIN1 localizes right at the point of presynaptic communication and may be precisely regulating neurotransmitter vesicle release brings us much closer to understanding how BIN1 could exert its function as a common risk factor for Alzheimer’s disease,” Dr. Thinakaran said. “We suspect it helps control how efficiently neurons communicate and may have a profound impact on memory consolidation – the process that transforms recent learned experiences into long-term memory.”

The research team created a mouse model in which the BIN1 gene was selectively inactivated, or knocked out, to characterize the protein’s normal function in the brain. In particular, they used advanced cell and molecular biology techniques to investigate the role of BIN1 in regulating synapses associated with learning and memory.

Peering into the brain, one synapse at a time: Electron micrograph shows selected region of a mouse brain hippocampus, the brain area responsible for learning and memory. A single synapse is marked with the yellow outline. | Image courtesy of Gopal Thinakaran, USF Health Morsani College of Medicine

To frame the study results, it helps to know that a healthy human brain contains tens of billions of brain cells (neurons) that process and transmit chemical messages (neurotransmitters) across a tiny gap between neurons called a synapse. In the Alzheimer’s disease brain, this synaptic communication is destroyed, progressively killing neurons and ultimately causing a steep decline in memory as well as other signs of dementia. Individuals most susceptible to developing full-blown Alzheimer’s in later life are those who lose the most synapses, Dr. Thinakaran said.

Among the Cell Reports study highlights:

• Loss of BIN1 expression in neurons leads to impaired spatial learning and memory. That is, the deficit alters how effectively information about surrounding environmental space is acquired, stored, organized and used. The BIN1 knockout mice had significantly more difficulty than controls in finding the hidden platform in a Morris water maze.
• Further analysis found that BIN1 is primarily located on neurons that send neurotransmitters across the synapse (presynaptic sites) rather than residing on those neurons that receive the neurotransmitter messages (postsynaptic sites). Synaptic transmission in the hippocampus, a brain region associated primarily with memory, showed deterioration in the release of neurotransmitters from vesicles. Vesicles are bubble-like carriers that transfer neurotransmitters from presynaptic to postsynaptic neurons.
• The BIN1 deficiency was associated with reduced density of synapses and a decrease in the number of synaptic clusters in the knockout mice compared to controls.
• 3-D electron microscopy reconstruction of the synapses showed a significant accumulation of docked and reserve pools of synaptic vesicles in the BIN1 knockout mice. That indicates slower (less successful) release of neurotransmitters from their vesicles, the researchers suggest.

Super-resolution imaging of BIN1 (green) combined with pre- and postsynaptic sites. White arrows at right indicate the overlap between BIN1 and synapsin, a protein involved in regulating neurotransmitter release at synapses. | Image courtesy of Gopal Thinakaran, USF Health Morsani College of Medicine, appeared first in Cell Reports (supplementary materials) doi.org/10.1016/j.celrep.2020.02.026

The study authors conclude that altogether their work highlights a non-redundant role for neuronal BIN1 in presynaptic regulation and “opens new paths for the future investigation of the precise role of BIN1 as a risk factor in Alzheimer’s disease pathophysiology.”

The research was supported by grants from the National Institutes of Health, the Cure Alzheimer’s Fund, and the Alzheimer’s Association, as well as fellowships from the BrightFocus Foundation and the Illinois Department of Public Health.

University of South Florida study suggests a new approach to inhibit the buildup of brain-damaging tau tangles associated with FTLD, Alzheimer’s disease and related dementias

TAMPA, Fla. (Feb. 18, 2020) — The protein β-arrestin2 increases the accumulation of neurotoxic tau tangles, a cause of several forms of dementia, by interfering with removal of excess tau from the brain, a new study by the University of South Florida Health (USF Health) Morsani College of Medicine found.

A beta-arrestin2 oligomer (foreground) shown within a nerve cell (background). Oligomerized beta-arrestin2 plays a central role in impairing tau clearance and the development of tau aggregates (magenta) in frontotemporal lobe degeneration and Alzheimer’s disease. | Image courtesy of artist Cynthia Greco and Eric Lewandowski (beta-arrestin2 protein modeling)

The USF Health researchers discovered that a form of the protein comprised of multiple β-arrestin2 molecules, known as oligomerized β-arrestin2, disrupts the protective clearance process normally ridding cells of malformed proteins like disease-causing tau. Monomeric β-arrestin2, the protein’s single-molecule form, does not impair this cellular toxic waste disposal process known as autophagy.

Their findings were first published Feb. 18 in the Proceedings of the National Academy of Science (PNAS).

The study focused on frontotemporal lobar degeneration (FTLD), also called frontotemporal dementia — second only to Alzheimer’s disease as the leading cause of dementia. This aggressive, typically earlier onset dementia (ages 45-65) is characterized by atrophy of the front or side regions of the brain, or both. Like Alzheimer’s disease, FTLD displays an accumulation of tau, and has no specific treatment or cure.

“Our research could lead to a new strategy to block tau pathology in FTLD, Alzheimer’s disease and other related dementias, which ultimately destroys cognitive abilities such as reasoning, behavior, language, and memory,” said the paper’s lead author JungA (Alexa) Woo, PhD, an assistant professor of molecular pharmacology and physiology and an investigator at the USF Health Byrd Alzheimer’s Center.

“It has always been puzzling why the brain cannot clear accumulating tau” said Stephen B. Liggett, MD, senior author and professor of medicine and medical engineering at the USF Health Morsani College of Medicine. “It appears that an ‘incidental interaction’ between β-arrestin2 and the tau clearance mechanism occurs, leading to these dementias. β-arrestin2 itself is not harmful, but this unanticipated interplay appears to be the basis for this mystery.”

The USF Health research team included, from left: Stephen Liggett, MD, senior author; David Kang, PhD, coauthor; and JungA (Alexa) Woo, PhD, lead author. | Photo by Freddie Coleman

“This study identifies beta-arrestin2 as a key culprit in the progressive accumulation of tau in brains of dementia patients,” said coauthor David Kang, PhD, professor of molecular medicine and director of basic research for the Byrd Alzheimer’s Center. “It also clearly illustrates an innovative proof-of-concept strategy to therapeutically reduce pathological tau by specifically targeting beta-arrestin oligomerization.”

The two primary hallmarks of Alzheimer’s disease are clumps of sticky amyloid-beta (Aβ) protein fragments known as amyloid plaques and neuron-choking tangles of a protein called tau. Abnormal accumulations of both proteins are needed to drive the death of brain cells, or neurons, in Alzheimer’s, although the tau accumulations now appear to correlate better with cognitive dysfunction than Aβ, and drugs targeting Ab have been disappointing as a treatment. Aβ aggregation is absent in the FTLD brain, where the key feature of neurodegeneration appears to be excessive tau accumulation, known as tauopathy. The resulting neurofibrillary tangles — twisted fibers laden with tau — destroy synaptic communication between neurons, eventually killing the brain cells.

“Studying FTLD gave us that window to study a key feature of both types of dementias, without the confusion of any Aβ component,” Dr. Woo said.

Monomeric β-arrestin2 is mostly known for its ability to regulate receptors, molecules on the cell that are responsible for hormone and neurotransmitter signaling. β-arrestin2 can also form multiple interconnecting units, called oligomers. The function of β-arrestin2 oligomers is not well understood.

The monomeric form was the basis for the laboratory’s initial studies examining tau and its relationship with neurotransmission and receptors, “but we soon became transfixed on these oligomers of β-arrestin2,” Dr Woo said.

Neurofibrillary tangles laden with tau (stained red) destroy synaptic communication between neurons, eventually killing the brain cells. This tau pathology is a feature of frontotemporal dementia, Alzheimer’s disease and several other dementias. | Image courtesy of David Kang

Among the researchers’ findings reported in PNAS:

– Both in cells and in mice with elevated tau, β-arrestin2 levels are increased. Furthermore, when β-arrestin 2 is overexpressed, tau levels increase, suggesting a maladaptive feedback cycle that exacerbates disease-causing tau.

–  Genetically reducing β-arrestin2 lessens tauopathy, synaptic dysfunction, and the loss of nerve cells and their connections in the brain. For this experiment researchers crossed a mouse model of early tauopathy with genetically modified mice in which the β–arrestin2 gene was inactivated, or knocked out.

– Oligomerized β-arrestin2 — but not the protein’s monomeric form – increases tau.  The researchers blocked β-arrestin-2 molecules from binding together to create oligeromized forms of the protein. They demonstrated that pathogenic tau significantly decreased when β-arrestin2 oligomers are converted to monomers

– Oligomerized β-arrestin2 increases tau by impeding the ability of cargo protein p62 to help selectively degrade excess tau in the brain. In essence, this reduces the efficiency of the autophagy process needed to clear toxic tau, so tau “clogs up” the neurons.

– Blocking of β-arrestin2 oligomerization suppresses disease-causing tau in a mouse model that develops human tauopathy with signs of dementia.

Above: Control nerve cells (green), in which oligomerized beta-arrestin-2 contributes to the accumulation of disease-causing tau (magenta). Below: When the neurons are transduced with b-arrestin2 oligomerization blocking viruses, tau pathology is dramatically reduced. | Images appearing in PNAS (Fig 6D) courtesy of Alexa Woo

“We also noted that decreasing β-arrestin2 by gene therapy had no apparent side effects, but such a reduction was enough to open the tau clearance mechanism to full throttle, erasing the tau tangles like an eraser,” Dr. Liggett said. “This is something the field has been looking for — an intervention that does no harm and reverses the disease.”

“Based on our findings, the effects of inhibiting β-arrestin2 oligomerization would be expected to not only inhibit the development of new tau tangles, but also to clear existing tau accumulations due to the mechanism of enhancing tau clearance,” the paper’s authors conclude.

The work is consistent with a new treatment strategy that could be preventive for those at risk or with mild cognitive impairment, and also for those with overt dementias caused by tau, by decreasing the existing tau tangles.

The study was supported in part by grants from the National Institutes of Health, National Institute on Aging.

The USF Health neurobiologist focuses on understanding genetic risk factors that may offer new therapy targets to delay or protect against age-related cognitive decline

There has been a steep rise in the number of Americans dying of Alzheimer’s disease – up 145 percent between 2000 and 2017  The burden of this neurodegenerative disease, which relentlessly diminishes the mind, is not only borne by those living more years in a state of disability and dependence before dying, but by the family members who care for them.

No treatments exist to cure or slow the progression of Alzheimer’ disease, the major form of dementia afflicting an estimated 5.8 million Americans.

“The goal of our research is to reduce the (brain) pathology leading to Alzheimer’s disease, by identifying targeted treatments to delay the onset of disease and protect cognitive function,” said Gopal Thinakaran, PhD, professor of molecular medicine and associate dean for neuroscience research at the USF Health Morsani College of Medicine. “Finding ways to extend cognitive function so that an older person is still able to continue their daily activities or recognize a loved one – even for five more years – would greatly benefit both those suffering from Alzheimer’s and their families or other caregivers.”

Gopal Thinakaran, PhD (center), who holds the Bagnor Endowed Chair in Alzheimer’s Research, with his research team at the USF Health Byrd Alzheimer’s Center.

Dr. Thinakaran, an internationally recognized Alzheimer’s disease researcher, joined the University of South Florida from the University of Chicago in August to help accelerate the interdisciplinary work of the USF Health Neuroscience Institute. That includes recruiting a critical mass of basic scientists who can complement the university’s ongoing Alzheimer’s research while also expanding efforts to translate laboratory findings into new therapies for other neurodegenerative disorders, including Parkinson’s disease, ataxias, ALS, and multiple sclerosis.

Probing molecular, cellular changes underlying pathology

In addition to his leadership role, Dr. Thinakaran oversees a laboratory at the Byrd Alzheimer’s Center where he uses cutting-edge cell biology techniques and mouse models to study the molecular and cellular processes underlying Alzheimer’s disease. His research is supported by more than $6.1 million in grants from the National Institutes of Health (NIH), National Institute on Aging.

With normal brain aging, people experience minor lapses of memory (i.e., forgetting where their keys were left, or the name of someone just met) and some reduced speed in processing information. But disruptions in attention, memory, language, thinking and decision-making that interfere with daily life are signs of dementia.

In addition to overseeing his own laboratory research, Dr. Thinakaran holds Morsani College of Medicine leadership roles as associate dean of neuroscience research and Neuroscience Research Institute associate director of research.

Dr. Thinakaran’s lab pursues findings on relatively new genes identified through genome-wide association studies to gain insights into the mechanisms of late-onset Alzheimer’s disease, which affects people age 65 or older and accounts for the overwhelming majority of cases. Recently, the group has been investigating the role of bridging integrator 1 (BIN1), the second most common genetic risk factor for late-onset Alzheimer’s (exceeded only by APOE). Approximately 40% of people with Alzheimer’s have one of three variations in the BIN1 gene – a glitch in a single DNA building block (nucleotide) that heightens their risk for the disease, Dr. Thinakaran said.

Pursuing a common risk factor for late-onset Alzheimer’s

BIN1, expressed in all the body’s cells, has been shown to play a role in suppressing tumors and in muscle development — but little is known about what the protein does in the brain. Dr. Thinakaran was among the first to embrace the challenge of pursuing how BIN1 contributes to Alzheimer’s disease risk at a time when most researchers focused on amyloid and tau, two proteins considered the primary drivers of Alzheimer’s pathology.

Now, his team and a few others across the country probe what goes wrong in Alzheimer’s patients who carry the BIN1 risk allele. They have already confirmed that BIN1 is present both in the brain’s nerve cells (neurons) and its non-neuronal cells, such as oligodendrocytes and microglia.

Biochemist Melike Yuksel, PhD, a postdoctoral scholar in Dr. Thinakaran’s lab

A healthy human brain contains tens of billions of neurons that process and transmit chemical messages (neurotransmitters) across a tiny gap between neurons called a synapse. Alzheimer’s disease severely disrupts this synaptic communication, eventually killing cells throughout the brain and leading to a steep decline in memory and other signs of dementia.

“The single biggest correlation with cognitive decline is the loss of these synaptic communication centers between neurons,” Dr. Thinakaran said, adding that individuals most susceptible to developing full-blown Alzheimer’s in later life are those who lose the most synapses.

In a study published March 10 in Cell Reports, Dr. Thinakaran and colleagues demonstrated for the first time that the loss of BIN1 expression impaired spatial learning and memory associated with remembering where things are located. The researchers used an Alzheimer’s disease “knockout” mouse model in which neuronal BIN1 expression was inactivated in the hippocampus, a brain region involved with higher cognitive functions.

Discovering a defect in brain cell communication

A lack of BIN1 leads to a defect in the transmission of neurotransmitters needed to activate the brain cell communication that allows us to think and behave, the researchers found. Further analysis found that BIN1 was primarily located in neurons that send neurotransmitters across the synapse (presynaptic sites) rather than residing on those neurons that receive the neurotransmitter messages (postsynaptic sites). The BIN1 deficiency was also associated with reduced synapse density; a back-up of docked vesicles, the tiny bubble-like carriers that transfer neurotransmitters from presynaptic to postsynaptic neurons; and likely slower release of the neurotransmitters from their vesicles.

“Our findings so far that BIN1 localizes right at the point of (presynaptic) communication and may be precisely regulating neurotransmitter vesicle release brings us much closer to understanding how BIN1 could exert its function as a risk factor (for Alzheimer’s disease),” Dr. Thinakaran said. “We suspect it helps control how efficiently neurons communicate.”

Peering into the brain, one synapse at a time. Electron micrograph depicting selected region of a mouse brain hippocampus, the brain area responsible for learning and memory. A single synapse is marked with the yellow outline.  The human brain is estimated to have trillions of these synapses, which transmit information from one neuron to the next.| Image courtesy of Gopal Thinakaran, PhD

Antibody-stained mouse brain with Alzheimer’s disease β-amyloid deposits. The amyloid precursor proteins within healthy nerve cells and swollen neuronal processes are depicted in blue. The late-onset Alzheimer’s risk factor BIN1 is shown in green, and a marker for brain glial cells responsible for neuroinflammation is shown in magenta.| Image courtesy of Gopal Thinakaran, PhD

Dr. Thinakaran’s team also became interested in investigating whether BIN1 risk variants can interfere with the protective capacity of glia (cells supporting neurons) to mount a full inflammatory response needed to clear toxins from the brain. His USF Health group will work with researchers at Emory University to further investigate why the absence of BIN1 may impair the brain’s removal of abnormal beta-amyloid protein associated with Alzheimer’s disease.

Exploring the type 2 diabetes connection

Collaborating with a coprincipal investigator at the University of Kentucky, Dr. Thinakaran also explores the molecular link between type 2 diabetes and Alzheimer’s disease progression. An Alzheimer’s mouse model created by the Thinakaran lab allows researchers to turn on, or switch off, production of the human hormone amylin in the pancreas.

Amylin is secreted by the pancreas at higher levels, along with insulin, as diabetes begins to develop. Small amounts of this excess amylin migrate from pancreatic cells into the bloodstream and can cross the blood-brain barrier, especially in older brains where the protective barrier becomes leakier. The amylin then mixes with the brain’s beta-amyloid, which eventually builds into the sticky amyloid plaques that are a hallmark of Alzheimer’s pathology. The researchers will test in their preclinical model whether this brain amylin elevates the risk for Alzheimer’s disease, and if reducing amylin in peripheral circulation can help prevent or slow damage to cognition.

Dr. Thinakaran with biological scientist Stanislau (Stas) Smirnou

Scientists are still trying to figure out why some people remain cognitively resilient throughout life despite having neuropathology that would otherwise cause dementia. On the horizon, Dr. Thinakaran said, integrating large databases of gene expression and individual cell types will help scientists drill deeper into what specific inflammatory, metabolic and neural circuit changes shift a normally aging brain to one in which the abilities to remember, think and reason abnormally accelerate.

At the same time, data on genetics and environment/lifestyle (including diet, physical and mental exercises, sleep patterns and uncontrolled cardiovascular risk factors such as hypertension, diabetes and high cholesterol) are being collected both for patients in various stages of Alzheimer’s disease and for older adults with healthy cognitive function. “Bridging these two sets of data will be extremely valuable in understanding what confers higher risk and delineating what can keep our brains healthy as we age,” Dr. Thinakaran said.

Fascinated by a field with unprecedented challenges

Dr. Thinakaran holds a PhD in molecular biology and genetics from the University of Guelph in Canada. He completed a postdoctoral research fellowship in neuropathology and was an assistant professor of pathology at Johns Hopkins University School of Medicine. Before joining USF Health, he was a professor of neurobiology at the University of Chicago, where he built one of the country’s leading laboratories investigating pathways responsible for Alzheimer’s disease pathology and neuronal dysfunction.

Known as an accomplished scientist and thought leader who does not hesitate to tackle uncharted territory, Dr. Thinakaran studied muscle differentiation as a PhD student. But, he soon realized that muscle research had advanced to a stage where it was unlikely he could make much of an impact. At that time (early 1990s) Alzheimer’s disease research was just gaining momentum in molecular and cellular biology and posing unprecedented challenges, he said.

Biological scientist Xiaolin Zhang, MS

Once Dr. Thinakaran’s interest in Alzheimer’s was sparked during his postdoctoral training at Johns Hopkins, he seized the opportunity to pursue the emerging area of neuroscience research. “In many ways the brain and its complexity as we age is the final frontier in understanding human behavior. We’re continuing to learn every day the basics of how this organ system works, and what goes wrong when it doesn’t,” he said. “It’s a field that still has great opportunities for the next generation of young minds to make a difference.”

Dr. Thinakaran has authored more than 140 peer-reviewed publications. He is associate editor for the journals Molecular Neurodegeneration and Genes and Diseases and an editorial board member for Neurodegenerative Diseases and for Current Alzheimer Research. He serves on several scientific review/advisory committees for federal, private and public institutions. Dr. Thinakaran has received numerous awards, including the Alzheimer’s Association prestigious Zenith Fellows Award supporting senior scientists pursuing new ideas to advance Alzheimer’s and dementia research.

Some things you may not know about Dr. Thinakaran

• Dr. Thinakaran combines his artistic talents of drawing and painting with his research. Andy Warhol-like microscopic art he created won a competition and was featured as the program cover for a brain research symposium at the University of Chicago. The multicolor montage of images depicts a mouse brain section (hippocampus) stained to visualize β-secretase, an enzyme critical for generating the hallmark Alzheimer’s disease β-amyloid pathology.
• He is married to neurophysiologist Angèle Parent, PhD, associate professor of molecular medicine at the Byrd Alzheimer’s Center. They have three children: Abigaël, a freshman and aspiring neuroscientist at the University of Chicago; Daphné, 14; and Cédric, 12.
• Dr. Thinakaran enjoys cooking authentic South Indian food and other international dishes with his family.

This microscopic brain art created by Dr. Thinakaran was featured on the program cover of a University of Chicago brain research symposium.

-Video by Allison Long, and photos by Freddie Coleman, USF Health Communications and Marketing

His team searches beyond the hallmark Alzheimer’s disease proteins for alternative treatments

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In his laboratory at the USF Health Byrd Alzheimer’s Center, neuroscientist David Kang, PhD, focuses on how different types of proteins damage the brain when they accumulate there. In the case of Alzheimer’s disease, decades of good science has zeroed in on amyloid and tau, as the two types of hallmark proteins driving the disease process that ultimately kills brain cells.

Dr. Kang and his team investigate molecular pathways leading to the formation large, sticky amyloid plaques between brain cells, and to the tau neurofibrillary tangles inside brain cells –including the interplay between the two proteins. But, he is quick to point out that amyloid and tau are “not the full story” in the quest to understand how normally aging brains go bad.

“Our goal is to understand as much of the entire Alzheimer’s disease process as possible and then target specific molecules that are either overactive or underactive, which is part of the drug discovery program we’re working on,” said Dr. Kang, professor of molecular medicine and director of basic research for the Byrd Alzheimer’s Center, which anchors the USF Health Neuroscience Institute.

Neuroscientist David Kang, PhD, (third from left)  stands with his team in his laboratory at the Byrd Alzheimer’s Center, which anchors the USF Health Neuroscience Institute.

Attacking dementia from different angles 

Dr. Kang’s group takes a multifaceted approach to studying the biological brain changes that impair thinking and memory in people with Alzheimer’s, the most common type of dementia, as well as Lewy body, vascular and frontotemporal dementias.

That includes examining how damaged mitochondria, the energy-producing power plants of the cell, contribute to pathology in all neurodegenerative diseases. “Sick mitochondria leak a lot of toxins that do widespread damage to neurons and other cells,” Dr. Kang said.

Dr. Kang’s team was the first to identify how mutations of a gene, called CHCHD10, which contributes to both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), cause both mitochondrial dysfunction and protein pathology called TDP-43. Their findings on the newly identified mitochondrial link to both neurodegenerative diseases were published in Nature Communications in 2017.

The role of selective degradation in ridding cells of abnormal proteins, old or damaged organelles (including mitochondria) and other debris is another key line of research pursued by Dr. Kang and colleagues.

A single stained nerve cell | Microscopic image courtesy of Kang lab

“We believe something more fundamental is going wrong in the brain during the aging process to tip the balance toward Alzheimer’s disease – beyond what we call proteinopathy” or deposits of malformed proteins like toxic amyloid and tau, said Dr. Kang, whose work is bolstered by nearly $8 million in grant funding from the National Institutes of Health (NIH), the Veterans Administration (VA merit awards) and the Florida Department of Health.

“I think one of the fundamental things happening is that the (cellular) plumbing system isn’t working to clear out all the accumulating junk,” he said. “That’s why we’re looking at the protective clearance mechanisms (autophagy and mitophagy) that would normally quickly remove misfolded proteins and dysfunctional mitochondria.”

Unfortunately, pharmaceutical trials to date have yielded no effective treatments for Alzheimer’s disease, the sixth leading cause of death in the U.S.  Most clinical studies have centered on developing medications to block or destroy the amyloid protein plaque formation, and a few have targeted the tau-containing neurofibrillary tangles. The five Alzheimer’s drugs currently available may provide temporary relief of symptoms, such as memory loss and confusion. But, they do not prevent or delay the mind-robbing disease as toxic proteins continue to build up and dismantle the brain’s communication network.

Lesson learned: The critical importance of intervening earlier

Some scientists argue that the “amyloid hypothesis” approach is not working. Dr. Kang is among those who maintain that amyloid plays a key role in initiating the disease process that leads to brain atrophy in Alzheimer’s – but that amyloid accumulation happens very early, as much as 10 to 20 years before people experience memory problems or other signs of dementia.

Early detection and treatment are key, Dr. Kang says, because as protein plaques and other lesions continue to accumulate in the brain, reversing the damage may not be possible.

“One reason we’ve been disappointed in the clinical trials is because so far they have primarily targeted patients who are already symptomatic,” Dr. Kang said. “Over the last decade we’ve learned that by the time someone is diagnosed with early Alzheimer’s disease, or even mild cognitive impairment, the brain has degenerated a lot. And once those nerve cells are gone they do not, for the most part, regenerate… The amyloid cascade has run its course.”

As protein plaques and other lesions continue to accumulate, becoming apparent with MRI imaging, reversing the damage may not be possible.  So, for anti-amyloid therapies – or even those targeting downstream tau – to work, patients at risk of Alzheimer’s need to be identified and treated very early, Dr. Kang said.

USF Health is recruiting healthy older adults with no signs of memory problems for a few prevention trials. A pair of Generation Program studies will test the effectiveness of investigational anti-Alzheimer’s drugs on those at high genetic risk for the disease before symptoms start. And, the NIH-sponsored Preventing Alzheimer’s with Cognitive Training (PACT) study is examining whether a specific type of computerized brain training can reduce the risk of mild cognitive impairment and dementias like Alzheimer’s disease in those age 65 and older.

To accelerate early intervention initiatives, more definitive tests are needed to pinpoint biomarkers that will predict Alzheimer’s disease development in genetically susceptible people. Dr. Kang is hopeful about the prospects.  His own team investigates how exosomes, in particular the lipid vesicles that shuttle proteins and other molecules from the brain into the circulating bloodstream, might be isolated and used to detect people at risk of proteinopathy.

“I think within the next five years, some type of diagnostic blood test will be available that can accurately identify people with early Alzheimer’s brain pathology, but not yet experiencing symptoms,” he said.

Graduate research assistant Yan Yan, a member of Dr. Kang’s research team, works at a cell culture hood.

Searching for alternative treatment targets

Meanwhile, Dr. Kang’s laboratory continues searching for other treatment targets in addition to amyloid and tau — including the enzyme SSH1, which regulates the internal infrastructure of nerve cells, called the actin cytoskeleton. SSHI, also known as slingshot, is needed for amyloid activation of cofilin, a protein identified by the USF Health neuroscientists in a recent study published in Communications Biology as a possible early culprit in the tauopathy process.

“Cofilin is overactive in the brains of Alzheimer’s patients so if we can inhibit cofilin by targeting slingshot, it may lead to a promising treatment,” Dr. Kang said.

Ultimately, as with other complex chronic diseases, Alzheimer’s may not be eliminated by a single silver-bullet cure.  Rather, Dr. Kang said, a combination of approaches will likely be needed to successfully combat the neurodegenerative disorder, which afflicts 5.8 million Americans.

“I think prevention through healthy living is definitely key, because brain aging is modifiable based on things like your diet as well as physical activity and brain exercises,” he said.  “Also, we need to focus on earlier diagnosis, before people become symptomatic, and develop next-generation drugs that can attack the disease on multiple fronts.”

Xingyu Zhao, PhD, a research associate in the Department of Molecular Medicine, is among the scientists in Dr. Kang’s laboratory studying the basic biology of the aging brain.

Fascinated by how the brain works — and malfunctions

Dr. Kang came to USF Health in 2012 after nearly 20 years as a brain researcher at the University of California San Diego, where he earned M.S. and PhD degrees in neurosciences and completed NIH National Research Service Award fellowships in the neuroplasticity of aging.

As an undergraduate Dr. Kang switched from studying engineering to a dual major in science/psychology. He began focusing on neurosciences in graduate school, he said, because tackling how the brain works and malfunctions was fascinating and always challenged him.

“With every small step forward, we learn something else about the basic biology of the aging brain,” said Dr. Kang, “It’s not just helpful in discovering what therapeutic approaches may work best against Alzheimer’s disease – we’re also learning more about other neurodegenerative conditions affecting the brain.”

In addition to leading day-to-day research operations at the Byrd Center and helping to recruit new Alzheimer’s investigators, Dr. Kang holds the Mary and Louis Fleming Endowed Chair in Alzheimer’s Research and serves as a research neurobiologist at the James A. Haley Veterans Haley Veterans’ Hospital.

He has authored more than 50 peer-reviewed journal articles on brain aging and Alzheimer’s disease research. A member of the NIH Clinical Neuroscience and Neurodegeneration Study Section since 2016, he has served on multiple national and international editorial boards, scientific panels and advisory boards.

Dr. Kang sits next to a computer monitor depicting stained microscopic images — a single neuron (far left) and the two hallmark pathological proteins for Alzheimer’s disease, tau tangles (center) and amyloid plaques (right).

Some things you may not know about Dr. Kang

• His parents were Presbyterian missionaries in Africa, so he spent nine years of his early life (third through 10^th grade) in Nigeria.
• Dr. Kang practices intermittent fasting, often forgoing breakfast and eating only within an 8-hour window. Animal studies indicate the practice may contribute to lifespan and brain health by improving cellular repair through the process of autophagy, he said. “Autophagy really kicks your cells’ plumbing system into gear to clear out all the waste.”

-Video and photos by Allison Long, USF Health Communications and Marketing

A USF Health preclinical study adds to mounting evidence about the interplay between genetics and environment in mental health

TAMPA, Fla. (June 10, 2019) – Researchers continue to dig for molecular clues to better understand how gene-environment interactions influence neuropsychiatric disease risk and resilience. An increasing number of studies point to a strong association between the FKBP5 gene and increased susceptibility to depression, anxiety, post-traumatic stress disorder and other mental health disorders.

Adding to the growing evidence, a new preclinical study by University of South Florida neuroscientists finds that anxiety-like behavior increases when early life adversity combines with high levels of FKBP5 – a protein capable of modifying hormonal stress response.  Moreover, the researchers demonstrate this genetic-early life stress interaction amplifies anxiety by selectively altering signaling of the enzyme AKT in the dorsal hippocampus, a portion of the brain primarily responsible for cognitive functions like learning and memory.

While more research is required, the study suggests that FKBP5 may be an effective target for treating anxiety and other mood disorders.

USF Health neuroscientists Laura Blair, PhD, (left) study senior author, and Marangelie Criado-Marrero, PhD, lead author.  The monitor displays a cross-sectional image of a mouse hippocampus.

The findings were published June 4 in the International Journal of Molecular Sciences.

“We know that the combination of genetic variations and environmental factors can make people either more or less susceptible to mental illness – even when they experience the same types of trauma,” said senior author Laura Blair, PhD, assistant professor of molecular medicine at the USF Health Byrd Alzheimer’s Center. Postdoctoral scholar Marangelie Criado-Marrero, PhD, was lead author of the study.

“We hypothesized that high FKBP5 and early life stress might yield neuropsychiatric symptoms through altered cellular stress response pathways in the brain.”

In a series of experiments, newborn mice overexpressing human FKBP5 in the forebrain were divided into two groups – one group was exposed to an early life stress (maternal separation), and the other was not.  Two control groups were comprised of stressed and non-stressed mice without brain overexpression of FKBP5. At two months, when the mice were young adults, an elevated-plus maze with open and closed arms was used to test anxiety-like behavior. Compared to all other groups, the mice with high FKBP5 and early life stress showed more anxiety as measured by their tendency to stay within enclosed areas of the maze rather than naturally explore all arms of the maze.

Dr. Criado-Marrero and Dr. Blair

The anxiety effect was more pronounced in the female mice than in males, an observation that aligns with sex differences noted in humans with anxiety disorders, Dr. Blair said.

The researchers also analyzed molecular changes in brains of the mice. They found that AKT signaling, specifically in the dorsal hippocampus, differed depending upon whether or not the mice with high FKBP5 had experienced maternal separation as newborns. AKT signaling – shown to be altered in Alzheimer’s disease and cancer as well as in mental health disorders — affects brain cell survival and metabolism, and the brain’s ability to adapt to new information.

“The AKT signaling pathway was inversely regulated as a result of early life stress. High FKBP5 normally decreases AKT signaling, but when early life stress was added to overexpressed FKBP5 that signaling activity increased,” Dr. Blair said. “Overall, our findings highlight the importance of stress and genes (like FKBP5) in modulating vulnerability to mood disorders and learning impairments.”

The USF Health researchers plan to next study the interaction of high FKBP5 and early life stress in older mice to determine how anxiety is affected by aging.

Slides of mouse neurons were analyzed to look for molecular changes in brain cells that correspond with changes in cognition.

The study was supported by grants from the NIH’s National Institute of Mental Health and National Institute of Neurological Disorders and Stroke.

Anxiety disorders are among the most common mental health conditions in the U.S, affecting 40 million adults, and nearly one in three of all adolescents will experience an anxiety disorder, according to the NIH.

-Photos by Allison Long, USF Health Communications and Marketing

The latest neuroscientist recruits will help USF Health accelerate new discoveries in Alzheimer’s disease and other neurological disorders 

The USF Health Neuroscience Institute, home of the Johnnie B. Byrd Sr., Alzheimer’s Center, brings together scientists and physicians to investigate the complexities of the brain and its impact on human health and behavior.

Internationally recognized Alzheimer’s disease researcher Gopal Thinakaran, PhD, has been recruited by USF Health to help accelerate the interdisciplinary work of its Neuroscience Institute (NSI), home of the Johnnie B. Byrd Sr., Alzheimer’s Center. Dr. Thinakaran, a professor of neurobiology at the University of Chicago, will join USF Health on Aug. 1.

University of Chicago neurophysiologist Angèle Parent, PhD, will also arrive here Aug. 1 as an associate professor of molecular medicine and member of the Byrd Alzheimer’s Center.

“Dr. Thinakaran and Dr. Parent are outstanding additions to our growing USF Health Neuroscience Institute,” said Charles J. Lockwood, MD, senior vice president of USF Health and dean of the Morsani College of Medicine. “Building upon the success of the Byrd Alzheimer’s Center, Dr. Thinakaran will help us advance interdisciplinary research among USF Health scientists and physicians looking at the brain in unique ways to accelerate discoveries to cure a broad range of neurological disorders, including Alzheimer’s and related dementias, Parkinson’s, ataxias, epilepsy, multiple sclerosis, ALS and stroke.  Moreover, Dr. Parent brings to the USF Health NSI a critical line of research into the mechanisms of memory dysfunction in dementia”

Gopal Thinakaran, PhD

Over the last decade Dr. Thinakaran built one of the country’s leading laboratories investigating the molecular and cellular processes underlying Alzheimer’s disease, the major form of dementia afflicting an estimated 5.8 million Americans.  He uses cutting-edge cell biology techniques and mouse models to probe nerve cell pathways responsible for Alzheimer’s disease pathology and neuronal dysfunction, with the goal of finding treatments to significantly reduce or delay cognitive decline.  Recently, he began exploring the molecular link between type 2 diabetes and Alzheimer’s disease progression.

Supported by $5.5 million in National Institutes of Health (NIH) grant funding, Dr. Thinakaran’s work has implications for other age-related and chronic neurodegenerative diseases that, while diverse, share some common characteristics such as abnormal protein aggregates and excessive nerve cell death.

At USF Health, Dr. Thinakaran will assume leadership roles as associate dean for neuroscience research and NSI associate director of research, in addition to his appointments as a professor of molecular medicine and the Bagnor Endowed Chair in Alzheimer’s Research. He will work closely with NSI CEO Harry van Loveren, MD; Stephen Liggett, MD, vice dean of research for the USF Health Morsani College of Medicine; and David Kang, PhD, director of basic research at the Byrd Alzheimer’s Center, to expand and integrate basic, translational and clinical neurosciences research across USF.

Dr. Parent studies how the brain remembers and what goes wrong with memory storage mechanisms in neurodegenerative diseases, focusing on communication between nerve cells (synaptic transmission) and neuronal plasticity. This April, Dr. Parent’s team published a study in Cell Reports demonstrating that sustained amyloid precursor protein (APP) signaling favors adaptive changes in the brain and prevents memory decline in an Alzheimer’s disease mouse model. She recently received a five-year, $1.75-million NIH grant to examine how differences in APP metabolism affect memory in sleep-disturbed Alzheimer’s mice.

Angèle Parent, PhD

An accomplished scientist who does not hesitate to explore uncharted territory, Dr. Thinakaran is also “a wonderful communicator, spokesman, and builder,” Dr. Liggett said. “As USF Health intensifies its effort to conquer Alzheimer’s disease and other dementias, as well as related neuroscience research, he will play an integral role in moving us forward. His combination of excellence in these skills is not that common, and I look forward to working with him to reach new heights in these research areas.”

NSI’s Dr. Van Loveren, chair of neurosurgery at MCOM, said Dr. Thinakaran recognizes the power of bringing different disciplines together to tackle the complexities of the brain and its impact on human health and behavior. “He is a scientific leader who understands the challenges of translating laboratory findings into new therapies that can target the root causes of neurodegenerative diseases – and the value of coordinated teamwork needed to bridge that gap.”

Both Dr. Thinakaran and Dr. Parent were recruited with the help of funding allocated through USF’s designation as a Preeminent State Research University.  The University of Chicago neuroscientists are the newest NIH-funded faculty members recruited since fall 2018 to strengthen and complement existing talent at the NSI’s Byrd Alzheimer’s Center. Others include:

• Krishna Bhat, MD, PhD, professor of molecular medicine and the Mary & Harry Goldsmith Endowed Chair in Alzheimer’s Disease, studies the genes and proteins that regulate the division of neuronal stem cells.
• Lianchun Wang, MD, professor of molecular pharmacology and physiology and USF Endowed Chair of Neurovascular Research, investigates the structure and function of a common linear polysaccharide, heparan sulfate, in inflammation, blood vessel development, stem cell biology, cancer and Alzheimer’s disease.
• Alexa Woo, PhD, assistant professor of molecular pharmacology and physiology, studies how multifunctional B-arrestin proteins contribute to tau pathology, a hallmark of Alzheimer’s and other neurodegenerative diseases in the brain.

Dr. Thinakaran said he was impressed by USF Health’s support of its well-established Byrd Alzheimer’s Center and the university’s drive to create an institute internationally known for its collaborative neurosciences research and training.

“I look forward to the opportunities to expand USF Health’s expertise in other neurological diseases and generate energy that will feed existing Alzheimer’s research,” he said.

USF Health study links Aβ-activated enzyme cofilin with the toxic tau tangles in major neurodegenerative disorders like Alzheimer’s disease

Neurofibrillary tau tangles (stained red) are one of the two major brain lesions of Alzheimer’s disease. Blue fluorescent stain (DAPI) depicts the nerve cell nuclei.

TAMPA, Fla. — The two primary hallmarks of Alzheimer’s disease are clumps of sticky amyloid-beta (Aβ) protein fragments known as amyloid plaques and neurofibrillary tangles of a protein called tau.  Abnormal accumulations of both proteins are needed to drive the death of brain cells, or neurons. But scientists still have a lot to learn about how amyloid impacts tau to promote widespread neurotoxicity, which destroys cognitive abilities like thinking, remembering and reasoning in patients with Alzheimer’s.

While investigating the molecular relationship between amyloid and tau, University of South Florida neuroscientists discovered that the Aβ-activated enzyme cofilin plays an essential intermediary role in worsening tau pathology.

Their latest preclinical study was reported March 22, 2019 in Communications Biology.

The research introduces a new twist on the traditional view that adding phosphates to tau (known as phosphorylation) is the most important early event in tau’s detachment from brain cell-supporting microtubules and its subsequent build-up into neurofibrillary tangles. These toxic tau tangles disrupt brain cells’ ability to communicate, eventually killing them.

David Kang, PhD, director of basic research at the Byrd Alzheimer’s Center, USF Health Neuroscience Institute, was senior author of the Communications Biology paper.

“We identified for the first time that cofilin binds to microtubules at the expense of tau – essentially kicking tau off the microtubules and interfering with tau-induced microtubule assembly. And that promotes tauopathy, the aggregation of tau seen in neurofibrillary tangles,” said senior author David Kang, PhD, a professor of molecular medicine at the USF Health Morsani College of Medicine and director of basic research at Byrd Alzheimer’s Center, USF Health Neuroscience Institute.

Dr. Kang also holds the Fleming Endowed Chair in Alzheimer’s Research at USF Health and is a biological scientist at James A. Haley Veterans’ Administration Hospital. Alexa Woo, PhD, assistant professor of molecular pharmacology and physiology and member of the Byrd Alzheimer’s Center, was the study’s lead author.

The study builds upon previous work at USF Health showing that Aβ activates cofilin through a protein known as Slingshot, or SSH1. Since both cofilin and tau appear to be required for Aβ neurotoxicity, in this paper the researchers probed the potential link between tau and cofilin.

The microtubules that provide structural support inside neurons were at the core of their series of experiments.

Alexa Woo, PhD, an assistant professor of molecular pharmacology and physiology at the USF Health Morsani College of Medicine, was the paper’s lead author.

Without microtubules, axons and dendrites could not assemble and maintain the elaborate, rapidly changing shapes needed for neural network communication, or signaling. Microtubules also function as highly active railways, transporting proteins, energy-producing mitochondria, organelles and other materials from the body of the brain cell to distant parts connecting it to other cells. Tau molecules are like the railroad track ties that stabilize and hold train rails (microtubules) in place.

Using a mouse model for early-stage tauopathy, Dr. Kang and his colleagues showed that Aβ-activated cofilin promotes tauopathy by displacing the tau molecules directly binding to microtubules, destabilizes microtubule dynamics, and disrupts synaptic function (neuron signaling) — all key factors in Alzheimer’s disease progression. Unactivated cofilin did not.

The researchers also demonstrated that genetically reducing cofilin helped prevent the tau aggregation leading to Alzheimer’s-like brain damage in mice.

An amyloid plaque (stained red), one of the two major brain lesions of Alzheimer’s disease, is shown here with the Aβ-activated enzyme cofilin (green) and nerve cell nuclei (blue).

“Our data suggests that cofilin kicks tau off the microtubules, a process that possibly begins even before tau phosphorylation,” Dr. Kang said. “That’s a bit of a reconfiguration of the canonical model of how the pathway leading to tauopathy works.”

Since cofilin activation is largely regulated by SSH1, an enzyme also activated by Aβ, the researchers propose that inhibiting SSH1 represents a new target for treating Alzheimer’s disease or other tauopathies. Dr. Kang’s laboratory is working with James Leahy, PhD, a USF professor of chemistry, and Yu Chen, PhD, a USF Health professor of molecular medicine, on refining several SSH1 inhibitors that show preclinical promise as drug candidates.

The research described in this Communications Biology paper was supported by grants from the VA, the NIH National Institute on Aging, and the Florida Department of Health.

Schematic of activated cofilin in tauopathy, which leads to pathological brain changes in people with Alzheimer’s disease and other major neurodegenerative disorders | Courtesy of Alexa Woo

-Photos by Allison Long, USF Health Communications and Marketing

USF Health Neuroscience Institute leaders accompany U.S. Rep. Gus Bilirakis on a tour of research laboratories in the Byrd Alzheimer’s Center, a centerpiece of the Institute.

Neurological diseases are growing at an unprecedented rate as Americans live longer and survive other chronic conditions like cardiovascular disease and cancer.

During U.S. Rep. Gus Bilirakis’ visit to the USF Health Neuroscience Institute on Aug. 24, the congressman was given an overview of the multidisciplinary research and clinical care that the University of South Florida conducts to help combat the human and economic burden of neurological diseases, including dementia, stroke, Parkinson’s disease and brain trauma.

The USF Health Neuroscience Institute, home of the Johnnie B. Byrd, Sr., Alzheimer’s Center, integrates three clinical departments — Neurology, Neurosurgery and Psychiatry – along with related basic and translational science departments. The Institute’s focus on consolidating disease-specific care for a wide spectrum of neurological diseases is intended to strengthen collaborative neuroscience research across USF and help accelerate promising discoveries from bench to bedside.

Laura Blair, PhD, assistant professor of molecular medicine, explains her team’s research on chaperone proteins that drive different states of the tau protein associated with Alzheimer’s and other neurodegenerative diseases. The USF Health researchers are identifying promising targets to help slow or prevent disease progression.

Bilirakis toured laboratories and the Johnnie B. Byrd, Sr., Alzheimer’s Center, the centerpiece of the Neuroscience Institute, with Stephen Liggett, MD, associate vice president for research at USF Health; Clifton Gooch, MD, chair of neurology at the USF Health Morsani College of Medicine (MCOM); and Glenn Currier, MD, chair of psychiatry and behavioral neurosciences at MCOM.  He also met with Robert Hauser, MD, director of the USF Parkinson’s Disease and Movement Disorders Center, which is designated a National Parkinson’s Foundation Center of Excellence.

These USF Health leaders spoke about the need for more federal resources directed toward helping advance early diagnosis and new treatments to delay, minimize and prevent nervous system disorders.

Robert Hauser, MD, (left) director of the nationally recognized USF Parkinson’s Disease and Movement Center, welcomes Bilirakis.

Among a few informational items they shared with the congressman:

• National Institute of Health grant funding does not cover the expense of high-tech equipment increasingly needed to do things like study single cells in the brain to understand the root cause of neurological diseases.
• 100 million Americans are afflicted with at least one neurological disease. A USF study led by Dr. Gooch and published last year in the Annals of Neurology found that the cost of diagnosed neurological disorders approaches a staggering $800 billion a year.
• More than half of MCOM’s $14.7 million in clinical trial revenue for FY 2018 was neuroscience related (neurology, psychiatry and neurosurgery).
• In addition to the Byrd Alzheimer’s Center and Parkinson’s Disease and Movement Disorders Center, other centers of excellence under the auspices of the USF Health Neuroscience Institute include stroke, epilepsy, multiple sclerosis (MS), Huntington’s disease, amyotrophic lateral sclerosis (ALS), ataxias with an emphasis on Friedreich’s ataxia, and aging and brain repair.
• USF Health Psychiatry and Behavioral Sciences continues to strengthen neurobiology research to discover new treatments for Alzheimer’s disease and abnormal brain development, as well as related mental disorders including autism. Current NIH-funded projects include studying ways to effectively deliver central nervous system drugs across the blood-brain barrier and testing the effectiveness of computer brain training games in protecting against cognitive decline.

USF Health’s Stephen Liggett, MD, (right) chats with Bilirakis in one of the laboratories at the Neuroscience Institute.

From left: Stephen Liggett, MD, USF Health associate vice president for research and Morsani College of Medicine vice dean for research; Congressman Gus Bilirakis, who represents Florida’s 12th District; Clifton Gooch, MD, chair of neurology; and Glenn Currier, MD, chair of psychiatry and behavioral neurosciences.

-Photos by Eric Younghans, USF Health Communications and Marketing