When a person experiences a traumatic brain injury, it can lead to lifelong neurological effects.
Researchers from the Indiana University School of Medicine and the University of California, Riverside are investigating how traumatic brain injuries and genetic risk factors can accelerate the development of Alzheimer’s disease and related dementias, which, according to the Alzheimer’s Association, nearly 6.9 million Americans 65 and older have.
The two institutions received a $3.5 million grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, to examine this connection.
“We are interested in the complex interplay between traumatic brain injury and genetic risk factors, and how these increase the susceptibility for individuals to develop Alzheimer’s disease and related dementias,” said Paul Territo, PhD, a professor of medicine at the IU School of Medicine and a co-principal investigator of the grant.
According to the CDC, an estimated 2.5 million people in the United States sustain a traumatic brain injury each year, and they can range from mild to severe. The most common causes are falls — especially for people over age 65 — and motor vehicle crashes.
There is growing clinical evidence that suggests that traumatic brain injuries can cause symptoms and the disease progression consistent with Alzheimer’s disease, said Territo, who is also a co-investigator of the Model Organism Development and Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD) consortium of experts at the IU School of Medicine, Jackson Laboratory, the University of Pittsburgh School of Medicine and Sage Bionetworks.
The consortium is developing the next generation of animal models, and MODEL-AD provides the key to translating research discoveries into new Alzheimer’s disease therapies. The consortium is one of several nationally funded studies at IU School of Medicine focused on finding treatment, prevention and an ultimate cure for Alzheimer’s disease.
In this study, Territo and Andre Obenaus, PhD, a professor of biomedical sciences at UC Riverside School of Medicine and co-principal investigator, and their teams will study three time periods in a 24-month lifespan of a mouse model: juvenile, midlife and late life.
The researchers will use cognitive behavioral outcomes, clinically relevant medical neuroimaging (PET/CT and MRI), immunopathology changes and tissue biomarkers to assess disease progression in mouse models with genetic risk factors of Alzheimer’s disease.
“This NINDS-funded grant will allow us to investigate the interactions of how Alzheimer’s disease genetics influence the development of traumatic brain injury in well characterized mouse models across three epochs of lifespan,” Obenaus said.
Territo said the researchers will leverage learnings and supporting evidence of the new mouse models developed by MODEL-AD and combine these with traumatic brain injury models, to fill an important gap in the understanding of how high-risk genes influence the susceptibility for disease progression in Alzheimer’s disease and related dementias.
Using translationally relevant medical imaging — a non-invasive way to assess both traumatic brain injury and Alzheimer’s disease — and combining these with biomarkers, which are biological molecules found in body fluids and tissues, the detection of abnormal processes and disease progression is possible, he said.
Scientists do not fully understand the long-term progression and biomarkers involved in traumatic brain injury. By combining these approaches, which links medical imaging, immunopathology and biomarkers into a comprehensive model, Territo said the team of researchers will gain significant improvements in their understanding of how traumatic brain injuries lead to Alzheimer’s disease and related dementias.