Yet another example of how biomarkers evolve, and could matter for litigation over alleged or actual injuries, as set out in a September 26, 2017 article in the Washington Post.
“By Rick Maese September 26 at 2:00 PM
In one of the biggest breakthroughs to date, researchers from Boston University School of Medicine have discovered a key biomarker for chronic traumatic encephalopathy that they hope marks the first step toward being able to diagnose and ultimately treat the neurodegenerative disease in a living football player.
Dr. Ann McKee, the neuropathologist credited with some of the most high-profile CTE diagnoses, said she was buoyed by the recent discovery, calling it “the first ray of hope” in a years-long effort to understand the disease.
“To me, it feels like maybe now we can start going in the other direction,” she said. “We’ve been going down, and everything has just gotten more and more depressing. And now it’s like, ‘Yeah, we’re going to actually find some answers here.’”
In a new study published Tuesday in the journal PLOS ONE, researchers from BU and the VA Boston Healthcare System studied the brains of 23 former football players who were diagnosed with CTE, in addition to those of 50 non-athletes who suffered from Alzheimer’s disease and 18 non-athlete controls. They found significantly elevated levels of a protein related to inflammation called CCL11 in the group of ex-players compared with the non-athletes. The levels were even higher in those who played the game longer.
“It’s a unique disease, and it’s going to have unique proteins that are modified in this disease, and this is the first indication that we’ve found one of the unique proteins,” said McKee, the director of BU’s CTE Center and senior author of the new study.
Of the 23 brains studied, 19 belonged to professional football players — including 18 who played in the NFL — and four others who reached the college level. The age range was 25 to 87 with a mean age of 62. The early findings do not necessarily allow researchers to determine how early they eventually might be able to detect the disease in a living person, McKee said. Of the samples studied, one came from a 49-year-old ex-player and another from a 53-year-old. Both of those subjects were diagnosed with Stage II (out of four stages) CTE.”
“CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in chronic traumatic encephalopathy (CTE) compared to Alzheimer’s disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 was measured with ELISA in the dorsolateral frontal cortex (DLFC) and CSF. CCL11 levels were significantly increased in the DLFC in subjects with CTE (fold change = 1.234, p < 0.050) compared to non-athlete controls and AD subjects with out a history of head trauma. This increase was also seen to correlate with years of exposure to American football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). Preliminary analyses of a subset of subjects with available post-mortem CSF showed a trend for increased CCL11 among individuals with CTE (p = 0.069) mirroring the increase in the DLFC. Furthermore, an association between CSF CCL11 levels and the number of years exposed to football (β = 0.685, p = 0.040) was observed independent of age (β = -0.103, p = 0.716). Finally, a receiver operating characteristic (ROC) curve analysis demonstrated CSF CCL11 accurately distinguished CTE subjects from non-athlete controls and AD subjects (AUC = 0.839, 95% CI 0.62–1.058, p = 0.028). Overall, the current findings provide preliminary evidence that CCL11 may be a novel target for future CTE biomarker studies.”