Penn researchers aim to uncover the underlying biological mechanisms of TBI-related neurodegeneration

A team of researchers led by Penn Medicine will investigate the link between traumatic brain injuries (TBI) and Alzheimer's disease and related dementias (ADRD) over the next five years with a $10 million grant from the National Institute of Neurological Disorders and Stroke (NINDS). Using an extensive tissue bank including over 1,000 samples, the researchers aim to uncover the underlying biological mechanisms of TBI-related neurodegeneration (TReND) from a variety of brain injury types. Researchers hope that by understanding TReND, they might gain further insight into how ADRD develops, and inform the development of better preventative measures and treatments. 

"We know that brain injuries increase the risk of Alzheimer's disease and related dementias, and they provide a unique opportunity to study neurodegeneration, as the imaging and cognitive testing required for their diagnosis provide a 'baseline' to compare to over time," said co-Principal Investigator, Douglas H. Smith, MD, director of the Center for Brain Injury and Repair and a professor of Neurosurgery at Penn. "By studying the effects of injuries over time, we hope to understand what happens biologically and structurally to the brain after injury that leads to neurodegeneration and hope that those findings also tell us how ADRD develop in general, even in individuals without a previous brain injury." 

This grant will support new initiative called Transdisciplinary Research Accelerating Neuropathology Studies and Facilitating Open Research Methods in TBI (TRANSFORM-TBI). In addition to expanding the tissue and imaging archives from the first phase, TRANSFORM-TBI will use samples to investigate why any TBI increases the risk of ADRD, even though brain injuries can vary widely from person to person. Researchers also aim to identify any factors that might increase the risk for developing ADRD. 

The team of 26 investigators across 12 sites aims to uncover the type and extent of neuropathological changes that emerge after TBI. They will evaluate the pathologies from a variety of types of TBI which could range from a single, severe injury, like from a car accident, to mild, repetitive injuries, which can occur while playing a contact sport. The team will also look at TBI, that results from military combat and intimate partner violence. 

Brain injuries vary widely from person to person, which can make it difficult to understand how they are associated with neurodegenerative disease later in life. By evaluating samples from different types of TBI and TBI with different causes, we hope to illuminate which types of brain injuries increase the risk of ADRD most, and hopefully use this information to tailor clinical trials for therapies to individuals' specific brain injuries." 

Edward B. Lee, MD, PhD, Co-Principal Investigator, Associate Professor of Pathology and Laboratory Medicine

TRANSFORM-TBI is the second phase of research to study TReND. In 2019, Smith, Lee and Willie Stewart of the University of Glasgow, UK, established CONNECT-TBI-;a program spanning 12 institutions to establish diagnostic criteria for TReND. To date, CONNECT-TBI has gathered clinical datasets and tissue archives from over 1,000 cases across participating centers. 

TRANSFORM-TBI is a collaboration between the Perelman School of Medicine and the University of Glasgow. It is supported by two NIH institutes, the National Institute of Neurological Diseases and Stroke (NINDS) and the National Institute of Aging (NIA)(U01NS137500-01). 

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