Researchers at the Icahn School of Medicine at Mount Sinai are pioneering the use of a new imaging agent used with positron emission tomography (PET) to detect and track the progression of repetitive traumatic brain injury in patients with a history of concussions.
The ability to actually see chronic traumatic encephalopathy (CTE) in living patients is particularly significant because the neurodegenerative disorder—associated with repetitive traumatic brain injury in athletes and soldiers—can only be definitively diagnosed in brain tissue after they are deceased.
“This has the potential to be used as a reliable biomarker,” says Sam Gandy, MD, PhD, Director of the Center for Cognitive Health and NFL Neurological Care at the Icahn School of Medicine at Mount Sinai. “If we can screen people who are exposed to CTE and find they have this pathology, they may want to curtail head injury exposure and arrest its progression.” In addition to including symptoms such as irritability and extreme mood swings, CTE is believed to be a precursor to various neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Lou Gehrig’s diseases.
Dr. Gandy and Dara L. Dickstein, PhD, Assistant Professor of Neuroscience, and Geriatrics and Palliative Medicine, recently coauthored a proof-of-concept study in Translational Psychiatry that used the new PET agent, or ligand, to examine a 39-year-old retired National Football League (NFL) player who had experienced 22 concussions. The patient exhibited agitation, impulsivity, sensitivity to light, periods of severe rage, and a decline in executive functioning, processing speed, and fine motor skills, as well as difficulty with working memory.
With the new ligand, Drs. Gandy and Dickstein were able to see evidence of CTE in the patient, which appeared as deposits of sticky tau protein in the brain that formed an irregular pattern of clumps rather than a normal pattern of strings. Pathologists believe a pattern of tau clumping is specific or “pathognomonic” for CTE. The disease involves widespread axonal disruption and the eventual degeneration of the neocortex, hippocampus and other limbic structures, and basal forebrain.
A link between brain injury and long-term health has gained greater attention in recent years, helped along by evidence of neurofibrillary tangles of tau protein, or tauopathy, that has been clinically confirmed in the postmortem brain tissue of former athletes and soldiers with a history of multiple head traumas.
Under the leadership of Drs. Gandy and Dickstein, and with funding from the Alzheimer’s Drug Discovery Foundation, Mount Sinai is one of the few medical centers researching the use of the new ligand in living patients who are believed to have CTE. The Mount Sinai team is currently studying 24 patients and plans to establish a clinical trial early next year that will employ the new ligand to identify CTE patients who might respond to an antitauopathy medicine manufactured by Cortice Biosciences Inc. The medicine is currently being studied at other medical centers for the treatment of Alzheimer’s disease, progressive supranuclear palsy, and corticobasal degeneration.
Whereas Alzheimer’s disease occurs in older patients who may be seen in their last years of life and then autopsied once they pass away, patients with CTE are often younger, making it more challenging for researchers to confirm their diagnoses through neuroimaging.
“This research is in its infancy,” says Dr. Dickstein. “Can the pathology be reversed or halted? This is something we have yet to determine, and these new tauopathy PET scans may be able to help in this endeavor.”
Dr. Gandy adds, “Until this new ligand was developed, there had been nothing available to monitor whether any therapeutic intervention might modify the tauopathy of CTE.”