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Characteristic Patterns of Proteins Found in Brains of Retired NFL Players Who Suffered Concussions

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(From left) Normal brain scan, suspected chronic traumatic encephalopathy (CTE) subject and Alzheimer’s case. More red and yellow demonstrates more abnormal brain proteins (tau and amyloid). High levels of the FDDNP signal (yellow/green) are seen in the midbrain (red central area) and the amygdalae (smaller red areas) in the suspected CTE subject. Also, the FDDNP signal is present throughout the cortex in the suspected CTE subject, which is where most of the FDDNP signal is located in the Alzheimer’s case.
Image: Courtesy of the David Geffen School of Medicine at UCLA

Using a new imaging tool, researchers found a strikingly similar pattern of abnormal protein deposits in the brains of retired NFL players who suffered from concussions. The imaging technique uses a chemical marker, called FDDNP, combined with a positron emission tomography (PET) scan and is helping scientists to take another step toward the early understanding of a degenerative brain condition called chronic traumatic encephalopathy (CTE), which affects athletes in contact sports who are exposed to repetitive brain injuries.

Researchers say the findings could help lead to the better identification of brain disorders in athletes and would allow doctors and scientists to test treatments that might help delay the progression of the disease before significant brain damage and the onset of symptoms that can include memory loss, confusion, progressive dementia, depression, suicidal behavior, personality change and abnormal gait and tremor.

Currently, CTE can only be diagnosed definitively following autopsy. To help identify CTE, doctors look for an accumulation of a protein called tau in the regions of the brain that control mood, cognition and motor function. Tau is also one of the abnormal protein deposits found in the brains of people with Alzheimer’s disease, although in a distribution pattern that is different from that found in CTE.
“The distribution pattern of the abnormal brain proteins, primarily tau, observed in these PET scans presents a ‘fingerprint’ characteristic of CTE,” says Jorge R. Barrio, PhD, professor of molecular and medical pharmacology.

In its study of 14 retired NFL players who had sustained at least one concussion each, the research team identified four stages of deposits that could signify early-to-advanced levels of CTE. “These different stages reflected by the brain marker may give us more insight into how CTE develops and allow us to track the disease over time,” says Vladimir Kepe, PhD, research pharmacologist in molecular and medical pharmacology.

After the study subjects were injected with the FDDNP marker, which binds to deposits of neurofibrillary tau “tangles” and amyloid beta “plaques,” the PET scans revealed that the imaging patterns of the retired football players showed tau-deposit patterns consistent with those that have been observed in autopsy studies of people with CTE. In addition, the areas in the brain where the patterns occurred were also consistent with the types of symptoms experienced by some of the study participants.

Compared with healthy people and those with Alzheimer’s, the former athletes had higher levels of FDDNP in the amygdala and subcortical regions of the brain, which are areas that control learning, memory, behavior, emotions and other mental and physical functions.

People with Alzheimer’s, on the other hand, had higher levels of FDDNP in areas of the cerebral cortex that control memory, thinking, attention and other cognitive abilities. And the athletes who had experienced more concussions also had higher FDDNP levels.
The scans of people with the highest levels of FDDNP binding in areas where tau accumulates in CTE also show binding in areas of the brain affected by amyloid plaques, which is consistent with autopsy findings indicating that this abnormal protein also plays a role in more serious cases of CTE.

“In Vivo Characterization of Chronic Traumatic Encephalopathy Using [F-18]FDDNP PET Brain Imaging,” Proceedings of the National Academy of Sciences, April 21, 2015


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