Dr. Geoffrey Manley, chief of neurosurgery at S.F. General, cautioned that the findings need to be verified.
Photo: Mike Kepka, The Chronicle
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For the first time, scientists think they have detected in living
patients a protein that accumulates in the brains of people suffering
from chronic traumatic encephalopathy, a neurodegenerative disorder tied
to repeated brain injuries that afflicts football players and
military veterans.
Doctors have only been able to diagnose CTE during autopsies based on the presence of a protein called tau, but UCLA researchers write in a paper published Tuesday that they believe they have identified tau in five living former NFL players.
The study was limited by the small number of participants, and the scientists could not definitively determine the protein was tau. But brain researchers said the findings open new doors to diagnosing people with chronic traumatic encephalopathy while they are still alive. That could lead to developing therapies to target tau and recognizing patients who could benefit from cognitive and psychological therapies early on.
"This is the first step toward identifying markers of this nature anytime post-injury while a person is still alive," said Stephanie Kolakowsky-Hayner, the director of rehabilitation research at Santa Clara Valley Medical Center, who did not work on the study.
"If you've got a way to diagnose this, if you can target it ahead of time, you might be able to alleviate it before it starts," she said.
The researchers injected the participants with a chemical marker called FDDNP that fastens to tangles of tau protein and beta amyloid plaques, which are signatures of Alzheimer's disease. They then performed PET scans - a form of imaging - on the patients to track the FDDNP.
Compared to scans of healthy brains, the scans of the athletes showed the marker gathering in the amygdala and subcortical regions - the same areas where scientists have found tau during autopsies. The regions are connected to emotion as well as motor and cognitive skills.
"The thing that was so striking was that the pattern in the brain was identical to the pattern in patients who had died and had CTE in their autopsy," said Dr. Gary Small, a professor of psychiatry and the director of the geriatric psychiatry division at the Semel Institute at UCLA.
What's more, the researchers found that a higher number of concussions correlated with a greater amount of FDDNP attachment, suggesting more buildup of the protein.
"We need to make sure that all the basic science behind this is solid and we know beyond a shadow of a doubt that we're looking at tau," he said.
He added that scientists are still trying to understand how the presence of tau may trigger the development of chronic traumatic encephalopathy.
In their report, the authors acknowledged that "the small sample size and lack of autopsy confirmation warrant larger, more definitive studies," but said that if their conclusions are validated, the method they used for their research could be replicated in patients to track protein formation as symptoms develop.
Small said the team is applying for more funding to expand the number of study participants and to be able to monitor them over the course of years.
"He just had normal aging - the question is why does one person develop problems and another does not?" Small said.
The other former players in the study were a linebacker and a center with mild cognitive impairment, a guard with dementia and depression, and a defensive lineman with mild cognitive impairment and depression.
Doctors have only been able to diagnose CTE during autopsies based on the presence of a protein called tau, but UCLA researchers write in a paper published Tuesday that they believe they have identified tau in five living former NFL players.
The study was limited by the small number of participants, and the scientists could not definitively determine the protein was tau. But brain researchers said the findings open new doors to diagnosing people with chronic traumatic encephalopathy while they are still alive. That could lead to developing therapies to target tau and recognizing patients who could benefit from cognitive and psychological therapies early on.
"This is the first step toward identifying markers of this nature anytime post-injury while a person is still alive," said Stephanie Kolakowsky-Hayner, the director of rehabilitation research at Santa Clara Valley Medical Center, who did not work on the study.
"If you've got a way to diagnose this, if you can target it ahead of time, you might be able to alleviate it before it starts," she said.
Study of 5 ex-NFL players
The study, which was published in the American Journal of Geriatric Psychiatry, looked at five retired NFL players between the ages of 45 and 73 who had histories of mood and cognitive problems.The researchers injected the participants with a chemical marker called FDDNP that fastens to tangles of tau protein and beta amyloid plaques, which are signatures of Alzheimer's disease. They then performed PET scans - a form of imaging - on the patients to track the FDDNP.
Compared to scans of healthy brains, the scans of the athletes showed the marker gathering in the amygdala and subcortical regions - the same areas where scientists have found tau during autopsies. The regions are connected to emotion as well as motor and cognitive skills.
"The thing that was so striking was that the pattern in the brain was identical to the pattern in patients who had died and had CTE in their autopsy," said Dr. Gary Small, a professor of psychiatry and the director of the geriatric psychiatry division at the Semel Institute at UCLA.
What's more, the researchers found that a higher number of concussions correlated with a greater amount of FDDNP attachment, suggesting more buildup of the protein.
More to be done
Researchers cannot be sure if the protein was tau because the chemical marker binds to other proteins as well. Dr. Geoffrey Manley, a neurosurgery professor at UCSF and chief of neurosurgery at San Francisco General, said the study raises interesting ideas but cautioned that the findings need to be verified."We need to make sure that all the basic science behind this is solid and we know beyond a shadow of a doubt that we're looking at tau," he said.
He added that scientists are still trying to understand how the presence of tau may trigger the development of chronic traumatic encephalopathy.
In their report, the authors acknowledged that "the small sample size and lack of autopsy confirmation warrant larger, more definitive studies," but said that if their conclusions are validated, the method they used for their research could be replicated in patients to track protein formation as symptoms develop.
Small said the team is applying for more funding to expand the number of study participants and to be able to monitor them over the course of years.
A genetic factor
Scientists are also looking at the role of genetics in CTE. Many athletes and veterans will take repeated blows to the head and not develop the condition. And one of the players studied, a former quarterback, appeared to have tau in his brain but only showed signs of aging and not chronic traumatic encephalopathy."He just had normal aging - the question is why does one person develop problems and another does not?" Small said.
The other former players in the study were a linebacker and a center with mild cognitive impairment, a guard with dementia and depression, and a defensive lineman with mild cognitive impairment and depression.
Drew Joseph is a San Francisco Chronicle staff writer. E-mail: djoseph@sfchronicle.com Twitter: @drewqjoseph
Read more: http://www.sfgate.com/health/article/A-clue-to-brain-disorder-before-death-4215667.php#ixzz2ImpbABTa
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