As the number of people with Alzheimer’s grows in the coming decades, more attention is being paid to people who develop dementia as a result of traumatic brain injuries (TBI). A recent study offers further insight into how exposure to explosive blasts in the military can lead to traumatic brain injury and later, neurodegeneration.
As many as 10 to 20 percent of returning veterans are estimated to have sustained mild TBIs as a result of blast exposure. TBIs can have long-term health consequences, and have been linked to developing neurological disorders later in life. One study estimated that experiencing a traumatic brain injury could increase the chances of developing dementia by up to 80 percent.
Chronic traumatic encephalopathy, or CTE, is the most common form of dementia that develops after sustaining repeated traumatic brain injuries.
This new study, published in Molecular Psychiatry and conducted by researchers at the Icahn School of Medicine at Mount Sinai and the James J. Peters VA Medical Center, combined an array of tests on both human and lab rat subjects to provide greater understanding on how blast exposure causes brain degeneration.
Using PET Scans to Dig Deeper into Traumatic Brain Injury
The researchers performed blood analysis and neuro-imaging on veterans exposed to between one and 50 improvised explosive device (IED) blasts on the battlefield. All of the veterans in the study had experienced chronic behavioral and cognitive issues.
Previous research has shown that when neurodegeneration occurs, two major chemical changes take place. The first is a grouping of tau, a protein linked to dementia and Alzheimer’s progression. The second is the leaking of a protein called neurofilament protein-light chain (Nf-L) from the brain into the blood.
Using PET scans that identify tau, the researchers found that 50 percent of the veterans displayed excessive buildup of tau in the frontal, parietal and temporal regions of the brain, areas where tau tends to clump in cases of TBI.
The study also included a rat model designed to mimic the blast exposure experienced by veterans. The lab rats were exposed to low-level blasts comparable to a mild TBI or blast exposure in humans. The rats exposed to the blasts displayed abnormal tau clumping in nerve cells and around blood vessels in cells known astrocytes, which are important in supporting nerve cells.
“We are fortunate to have access to both living humans and living rodent models so that we can conduct side-by-side comparisons of the clinical and microscopic changes that are common to both species related to traumatic brain injury,” Dr. Sam Gandy, a study author and director of the Center for Cognitive Health and NFL Neurological Care at the Icahn School of Medicine at Mount Sinai, said in a news release.
“As a result of these parallel studies in veterans and in the [rat] brain injury model, we are well on our way to the first clinical trials wherein first-in-class drugs will be evaluated for their safety and for their potential clinical benefit in relieving the anxiety, depression, memory disorders, and anger management issues that are associated with traumatic brain injuries,” Gandy continued.
Developing Earlier Diagnosis for CTE
Prior research conducted by Gandy examined PET scans of living athletes and veterans who had histories of TBI, and analyzed the behavior and presence of amyloid and tau proteins. These proteins are linked with the development of neurodegenerative diseases, including frontotemporal dementia, Alzheimer’s and CTE. At present, cases of CTE can only be proven postmortem, but both Gandy and Elder believe that their research may be a step towards discovering better methods of diagnosis while patients are alive.
“There are many young, otherwise healthy veterans who have suffered blast-related TBIs, some of them years in the past, who either aren’t getting better or, in some cases, are getting worse,” Elder said. “We don’t know why or how to identify those at greatest risk. The work in this study is a step towards answering those questions.”