Breakthrough: CTE Biomarker Could Lead to Treatments

New details surrounding chronic traumatic encephalopathy (CTE) are exponentially found, but continuously ominous.

The neurodegenerative condition was first defined in the early 2000s, when it began to be primarily diagnosed in deceased former National Football League (NFL) players. Since then, more and more former football players have been linked to it via autopsy.

In recent months, the Journal of the American Medical Association reported that 110 of 111 (99%) of studied deceased former NFL players suffered from the trauma-based condition. Then, Boston University researchers reported Aaron Hernandez had stage 3 advanced CTE in an autopsy following his suicide.

Another Boston University study from last month reported that youth tackle football players, who take up the contact form of the sport at a younger age, are notably more likely to suffer from cognitive impairments and depression as they age.

Once again, Boston University researchers shared new CTE-based findings this week. But it’s finally optimistic.

A new biomarker that could help researchers diagnose the disease in living patients may have been found in a joint study conducted by Boston University School of Medicine and VA Boston Healthcare System researchers.

Protein CCL-11 has been identified as an indication of CTE in the first comparative study of CTE and Alzheimer’s disease patients versus normal aging, Ann McKee, MD, professor of Neurology and Pathology, and director of Neuropathology Core for the Boston University CTE Center, told MD Magazine.

McKee, the study’s senior author, said the biomarker study is researcher’s first foray into looking at the potential mechanisms of the disease’s development.

“One mystery of the disease is that it’s caused by mild repetitive trauma,” McKee said. “Even after, once the disease is established, it seems to slowly progress through the lifetime.”

The team studied 23 former college and professional football players’ brains, compared to 50 nonathletes Alzheimer’s patient brains and 18 nonathlete controls’ brains.

CCL-11 levels were notably higher in CTE patient brains than the baseline returns found in Alzheimer’s and control patient brains, and a correlated rate of elevation between the protein and number of years the CTE patient had played football was also noted.

A focal abnormality in the front cortex of patients is noted in even the youngest patients, McKee said. The abnormality is not only composed of tau protein deposit, but lesions surrounded by small blood vessels leaking proteins into the brain. These lesions are also neighbored “enormous inflammatory response,” McKee said.

“There’s a direct relationship between inflammation and tau pathology,” McKee said. “One of the good possibilities for this progression is this persist — this sort of out-of-control inflammatory response.”

Though it’s currently conjecture, if CCL-11 proves to be a reliable CTE biomarker, there’s good reason to think it can be found in the small blood vessels leaking to the brain, McKee said. Therefore, it could turn out to be a characteristic protein found in living patients’ spinal fluid through procedures.

McKee, who up until this discovery had been seeking out CTE’s characterizations and relying on deceased patients to do so, was excited to share the potential biomarker.

“It’s the first time we could’ve possibly developed a biomarker for this disease,” McKee said. “Not only may we find ways to detect the disease, it could give us ways to treat the disease.”

That said, McKee expressed hope for additional characteristic biomarkers to be found, in order to give CTE its own distinctive diagnosis process in living patients. After that, treatments can be considered. But before that, “stylistic changes” can be considered for tackle football, McKee said.

The researcher noted practicing without a helmet, or taking up the sport at an older age could lessen a player’s chances of developing CTE.

“There are things you can do besides ban football,” McKee said.

Moving forward, McKee is interested in uncovering the role of genetics in inflammatory response of patients. Studies proving correlation could lead to doctors advising particular people from considering activities other than football.

Boston University CTE Center researchers are also conducting 3 ongoing studies related to next steps. The Diagnosing and Evaluating Traumatic Encephalopathy Using Clinical Tests (DETECT) study, funded by the National Institutes of Health (NIH), is focused on developing diagnostic tests. According to the center’s website, subjects will undergo MRI scans, MRS scans, blood tests, and protein measures of spinal fluid.

Though that study’s enrollment period has ended, another 2 related studies on CTE and neurodegeneration are seeking subjects as of this week. Football players have reached out to volunteer in the hundreds, McKee said, as the public interest in uncovering the condition has grown with the rate of discoveries.

But — for a condition that’s linked not just to football players, but military personnel as well — only the tip of the iceberg has been uncovered.

“That’s why we need to get on top of this,” McKee said. "We really have to get after this, because it’s happening.”

The study, "CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer’s disease," was published online in PLOS One this week.