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A new imaging technique has allowed detection of tau protein abnormalities in the concussed brains of living retired football players that are identical to the autopsy findings of chronic traumatic encephalopathy (CTE) in deceased athletes, researchers reported.
Positron emission tomography (PET) scanning using a tracer for tau protein known as FDDNP found significantly higher binding values among retired players than in controls in several regions of the brain, including the amygdala (1.30 versus 1.14, P=0.03) and caudate (1.48 versus 1.23, P=0.03), according to Gary W. Small, MD, of the University of California Los Angeles, and colleagues.
In addition, the tau binding values were highest in the players who had experienced the most concussions during their careers, which "suggests a link between the players' history of head injury and FDDNP binding," the researchers wrote in the February American Journal of Geriatric Psychiatry.
"If this research continues in the direction we expect, it would have a big impact on the early detection of this condition, helping us to develop interventions that could delay the onset of symptoms," Small told MedPage Today.
But it will be important to replicate these findings in larger studies, experts cautioned.
"If indeed it is sensitive and specific enough for tau, it would be extremely exciting and hugely important, but this was only five players," said Robert Cantu, MD, of Emerson Hospital in Concord, Mass., and co-director of Boston University's Center for the Study of Traumatic Encephalopathy.
The list of athletes who experience multiple concussions during routine play and then develop cognitive, behavioral, and mood disturbances, which in some cases lead to suicide, continues to grow, and some 4,000 former National Football League players are suing the league, claiming that the risks of repetitive head injury were long downplayed.
Autopsy findings in players who died have included deposits of phosphorylated tau in neurofibrillary tangles, as well as diffuse injury to axons and abnormalities of white matter.
Despite the increasingly widespread recognition that players with multiple concussions are experiencing severe consequences, research into the resulting condition has been hindered by the fact that no diagnostic test has been available that could identify changes before death.
Small and his colleagues developed the tau tracer FDDNP (2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile) with the goal of detecting the presence of tau tangles and amyloid plaque in the living brains of Alzheimer's disease patients.
They found that with this PET technique they could differentiate Alzheimer's patients from those with milder forms of cognitive impairment or normal changes of aging.
In the current study, they performed neuropsychiatric evaluations of five former players who exhibited mood or cognitive symptoms clinically, and then used PET scanning with FDDNP to examine their brains.
The players had played various positions, including quarterback, center, and defensive lineman, with careers ranging from 10 to 16 years.
The researchers also assessed five controls who were matched for age, body mass index, family history of dementia, and educational attainment.
Cases and controls were both about 60 years of age. The affected players had significantly higher scores on the Hamilton Rating Scale for Depression (8 versus 0) than controls, and also showed a trend toward lower scores on the Mini-Mental State Examination, which evaluates cognitive impairment.
Higher signals for tau binding were seen in a number of subcortical regions in cases compared with controls, including: Putamen, 1.47 versus 1.20 (P=0.05)Thalamus, 1.48 versus 1.29 (P=0.03)Subthalamus, 1.45 versus 1.25 (P=0.03)Midbrain, 1.31 versus 1.14 (P=0.03)Cerebellar white matter, 1.15 versus 1.09 (P=0.05)
The researchers explained that this pattern of findings was different from that seen in patients with cognitive difficulties but no history of head trauma, in elderly depressed patients, and in those with Alzheimer's disease.
While FDDNP can bind to both tau and amyloid in Alzheimer's patients, only a minority of CTE autopsies have identified amyloid plaques, suggesting that in these players, the high levels of binding signals are specific for tau.
"Using a tau marker for detection and tracking of neurodegenerative disease is critically important because severity of tau load, rather than amyloid burden, correlates with rates of neuronal loss," the researchers explained.
They noted that their findings should be interpreted with caution because of the limited number of players and the possibility that other factors such as genetics and overall cerebrovascular health might influence outcomes.
Small expressed hope that, if this diagnostic approach proves accurate in larger numbers, it may open the way to possible treatments.
"We know that inflammation is important both in Alzheimer's disease and traumatic brain injury, and in Alzheimer's we're testing anti-inflammatory and anti-tau treatments," he said.
"We also know that lifestyle choices and everyday health habits including diet, exercise, and stress management are important in protecting our brains," he added.
The study was supported by the Brain Injury Research Institute, the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research, the Ahmanson Foundation, and the Parlow-Solomon Professorship.
Two of the authors are among the inventors of a technique for labeling beta-amyloid plaques and neurofibrillary tangles and have received royalties. They also have received fees from several companies, including Janssen, Lilly, Novartis, Pfizer, Bristol-Myers Squibb, and Siemens.
Primary source: American Journal of Geriatric Psychiatry
Source reference:
Small G, et al "PET scanning of brain tau in retired National Football League players: Preliminary findings" Am J Geriatr Psychiatry 2013; 21: 138-144.
Nancy Walsh
Staff Writer
Nancy Walsh has written for various medical publications in the United States and England, including Patient Care, The Practitioner, and the Journal of Respiratory Diseases. She also has contributed numerous essays to several books on history and culture, most recently to The Book of Firsts (Anchor Books, 2010).
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