Miller School Researchers Receive State Funding for Multifaceted Alzheimer’s Disease Study
Article Summary
- Using its Team Science approach, a multidisciplinary team of Miller School researchers are using Florida Department of Health funding to conduct four Alzheimer’s disease investigations.
- The studies will include the development of imaging tools and biomarkers to detect Alzheimer’s disease at an early stage, therapeutic intervention to reduce brain inflammation in the brain and an analysis of brain-gut dysfunctions.
- Researchers will look at Alzheimer’s disease at the molecular level to determine if therapies are ready for clinical trials.
A multidisciplinary team of Miller School of Medicine researchers will explore four related approaches to diagnosing and treating Alzheimer’s disease, thanks to a major grant from the Florida Department of Health.
“We are very excited to receive $1 million in state funding to support new collaborations in discovery, translational and clinical research targeting neurodegenerative disorders,” said W. Dalton Dietrich, Ph.D., scientific director of The Miami Project to Cure Paralysis. “One of Florida’s biggest medical needs is new strategies to diagnose and treat neurodegenerative diseases. Our researchers have been studying the mechanisms of protection and repair in traumatic brain injuries, spinal cord injuries, strokes and neurodegenerative diseases for many years, and this award reflects our leading-edge scientific and clinical work in these fields.”
The team science award will support studies on:
- The development of new imaging tools and biomarkers to detect Alzheimer’s disease at an early stage
- Therapeutic intervention to reduce inflammation in the brain
- An analysis of brain-gut dysfunctions in some patients with neurodegenerative disorders
The Miller School team includes researchers from the Miami Project to Cure Paralysis, the Departments of Neurology, Neurological Surgery, Psychiatry and Behavioral Sciences, Pathology and Laboratory Medicine, Physiology and Biophysics and the Center for Cognitive Neuroscience and Aging.
“We are using experimental models, cells in culture and human tissue samples to understand Alzheimer’s disease pathology at the molecular level and see whether a new therapy, currently being manufactured, is ready for testing in clinical trials,” said Pablo de Rivero Vaccari, Ph.D., associate professor of neurological surgery at the Miller School.
Genomic Analysis of the Brain
Using state-of-the-art spatial genomic analysis of brain tissues, one project will focus on a potential new diagnostic biomarker for Alzheimer’s disease. The researchers will evaluate the importance of an adaptor molecule in inflammasome signaling, a process that activates the immune system’s inflammatory response.
“We will investigate how the expression of inflammasome proteins advances as neurodegenerative changes progress into other regions of the brain,” said Regina Vontell, Ph.D., assistant professor of neurology and associate director of the University of Miami Brain Endowment Bank.
Dr. Vontell is leading the project with Dr. Vaccari, using brain bank tissues from normal aging and intermediate Alzheimer’s disease donors.
“Neuropathological changes occur in distinct regions of the brain as dementia advances,” added Dr. Vontell. “Correlating inflammasome proteins with those changes is fundamental to map out the effectiveness of IC100, a monoclonal antibody, as well as other pathological issues.”
Biomarkers in People at Risk for Alzheimer’s
A second project will focus on the development and testing of highly sensitive surrogate blood biomarkers for the diagnosis of early Alzheimer’s disease in Black/African and Hispanic/Latino populations facing a higher risk for dementia.
“For these investigations, blood biomarker findings will be correlated with sensitive measures of early stages of cognitive decline,” said David Loewenstein, Ph.D., professor of psychiatry and behavioral sciences and neurology at the Miller School and director of the Center for Cognitive Neuroscience and Aging.
He is leading the project with Rosie Curiel Cid, Psy.D., associate professor of clinical psychiatry and behavioral sciences at the Miller School, and Dr. Vaccari.
“We will analyze the roles of inflammasome, powerful Alzheimer’s biomarkers, and other plasma biomarkers,” said Dr. Loewenstein, also associate director of the 1Florida Alzheimer’s Disease Research Center. “Cognitive stress tests developed at the Miller School, along with neuroimaging and the ability to follow our sample in time will provide powerful data on the factors that converge to initiate the Alzheimer’s disease cascade. We are very excited about this innovative team science initiative.”
Early Alzheimer’s Detection Tracer
A third project involves the development and testing of a novel positron emission tomography (PET) diagnostic imaging agent for early detection of Alzheimer’s disease. Robert Keane, Ph.D., professor of physiology and biophysics and neurological surgery, and Daniel Bilbao, Ph.D., M.B.A., research assistant professor of pathology, are working on this task with Dr. Dietrich, Dr. Vaccari and members of the Department of Nuclear Medicine.
“Currently, PET scans are using tracers for amyloid-beta proteins in the brain,” said Dr. Keane. “However, this is not an ideal therapeutic target for improving care. Therefore, we are developing a PET tracer to image inflammasome proteins in experimental models prior to testing in humans.”
Dr. Keane added that the team’s recent findings have shown inflammasome is involved in Alzheimer’s disease and traumatic encephalopathy, encouraging this study of new tracers to address current limitations.
Brain-Gut Connections
Some Alzheimer’s patients and traumatic brain injury survivors suffer from acute and chronic gut complications. A Miami Project team led by Nadine Kerr, Ph.D., assistant professor of neurological surgery at the Miller School, Helen Bramlett, Ph.D., professor of neurological surgery at the Miller School and Dr. Dietrich will evaluate a novel mechanism underlying the brain-gut dysfunction.
“Our group has studied gut-brain dysfunctions after stroke and this project extends our work into similar problems among traumatic brain injury and Alzheimer’s patients,” said Dr. Kerr. “We hope to gain important translational information for brain-injured patients who are genetically predisposed to Alzheimer’s disease and advance the development of therapeutic interventions for gut-brain complications.”
Dr. Kerr said the team will use experimental models to clarify the role of extracellular vesicles released by the injured brain as they circulate through the body and produce multi-organ problems. This process can also increase the risk of developing neurodegenerative disorders.
“Together, these highly collaborative investigations will work on novel strategies for the early diagnosis and treatment of Alzheimer’s disease and other neurodegenerative disorders,” Dr. Kerr said. “We thank the state of Florida for this important funding.”
Tags: Alzheimer's disease, Dr. David Loewenstein, Dr. Nadine Kerr, Dr. Pablo de Rivero Vaccari, Dr. Regina Vontell, Dr. Robert Keane, Dr. Rosie Curiel Cid, Dr. W. Dalton Dietrich III, team science