A traumatic brain injury, or TBI, is caused by a contusion to the head that can result in brain damage. This type of injury, combined with the inherited genetic risk factors, can result in the accelerated development of Alzheimer’s disease and related dementia, or ADRD. TBIs range from mild to severe, with the majority being mild. They are especially common in adolescents who play contact sports and in older people who fall more often as they get older. Regardless of the source, TBI and how it develops into ADRD is an understudied area of research.
A $3.5 million grant to the University of California, Riverside and Indiana University, from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, will now investigate how TBI at different ages and genetic risk factors lead to ADRD .
There is some literature suggesting that traumatic brain injury may progress to Alzheimer’s disease in some cases or precipitate disease-like symptoms.”
Andre Obenaus, professor of biomedical sciences at UCR’s School of Medicine and principal investigator of the three-year grant
“We are interested in the complex interplay between TBI and genetic risk factors, and how these increase individuals’ susceptibility to developing Alzheimer’s disease and related dementias,” said Paul Territo, professor of medicine at Indiana University School of Medicine, and co . -principal investigator of the proposed work.
Using rodents, Obenaus, Territo and their teams will study three different time periods in a mouse’s 24-month lifespan: the juvenile age, which is postnatal day 17; midlife, i.e. when the mice are 8-9 months old; and late life, that is, when the mice are 12 months old. The researchers will use cognitive behavioral outcomes, clinically relevant medical neuroimaging (PET/CT, MRI), immunopathological changes and tissue biomarkers to assess disease progression.
“This system will allow us to investigate the interactions of how genetics and TBI in well-characterized models across three epochs of the lifespan influence progression to ADRD,” Obenaus said.
An expert in traumatic brain injury, stroke, Alzheimer’s disease and epilepsy, Obenaus has worked on traumatic brain injury for more than twenty years. He joined the UCR faculty in March 2024. He is a member of a National Institute of Aging-funded consortium, MODEL-AD, charged with building better models of Alzheimer’s disease in mice. The consortium is based at UC Irvine.
An expert in Alzheimer’s disease, biomarker development, and therapeutic agent testing, Territo has worked in both the academic and pharmaceutical industries to develop rigorous and reproducible systems to monitor disease progression and evaluate therapeutic response. These areas of expertise are extensively leveraged in the MODEL-AD consortium, where its laboratory characterizes mouse models of ADRD and subsequently conducts therapeutic evaluation of new drug candidates.
“We hope to identify early on the individual mice that will develop an Alzheimer’s-like phenotype,” Obenaus said. “We do not expect that all mice will develop Alzheimer’s disease, but a certain subset of mice will. The goal is to identify the combinations of risk genes and the timing of TBI that modulate the fluid and imaging biomarkers involved, so that early intervention is possible to prevent or slow the progression of Alzheimer’s disease.”
Medical imaging is the only non-invasive way to assess both TBI and ADRD. In combination with fluid biomarkers, which are biological molecules found in body fluids and tissues, detection of abnormal processes or disease progression is possible. Obenaus explained that a lot of research has been done on TBI, but scientists still don’t fully understand the long-term progression and the biomarkers involved. Territo highlighted the combined power of linking readouts from medical imaging, immunopathology, and fluid biomarkers in a comprehensive model, which will yield significant improvements in predictive validity in both TBI and ADRD.
“We now have sufficient technical expertise in this area to address this research problem, allowing us to better define TBI and its role in initiating Alzheimer’s disease,” Obenaus said. “Additionally, there has been a wealth of research over the past two decades on the two key proteins, tau and amyloid, which are thought to disrupt communication between brain cells and lead to ADRD.”
Obenaus and Territo said data from the research project will be aggregated and made freely available to other researchers through the NIH Open Science framework.
They will be joined in the research project by Adam Godzik and Devin Binder, professors of biomedical sciences at the UCR School of Medicine. A research team from the Uniformed Services University of the Health Sciences in Maryland, led by Dr. Denes Agoston, will also work on the project. Also joining the team is Talin Babikian, a neuropsychologist at UCLA who has extensive experience with TBI and its progression. Graduate students and postdoctoral researchers from UCR and Indiana University will also work on the research project.
Research reported in this press release was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number RF1NS138032. The contents do not necessarily represent the official views of the National Institutes of Health.