A tau radiotracer may be able to detect chronic traumatic encephalopathy (CTE) while patients are still alive, researchers reported.
A 39-year-old retired NFL player who had 22 concussions over the course of his 11-year career -- four of which resulted in loss of consciousness -- and recent behavioral and cognitive complaints had a pattern of tau deposition in the brain that was consistent with CTE, , of Mount Sinai in New York City, and colleagues reported online in .
Action Points
- Tau imaging of the brain of a 39- year-old retired football player who suffered multiple concussions and had recent behavioral and cognitive complaints showed tau deposition consistent with chronic traumtic encephalopthy (CTE), suggesting that a tau radiotracer may be able to detect (CTE) while patients are still alive.
- Note that while the diagnosis of CTE can currently only be definitively established postmortem, the deposition of tau in cortical gray matter/white matter junctions is the hallmark of CTE and distinguishes it from Alzheimer's and other tauopathies.
"We saw [tau] outlining the wrinkles of the brain near the surface, and that is typical for CTE," Gandy told 木瓜直播. "We haven't seen that in other tau diseases. We feel this can serve in lieu of having the post-mortem correlation."
The team used [18F]T807/AV1451 with PET imaging to look at where tau had been accumulating in the patient's brain. This is the same tracer, made by Philadelphia-based Avid Pharmaceutical, that has been used to image tau in the brains of Alzheimer's disease patients.
The patient had first been seen by , of Boston University's CTE study group, about 5 years ago and had been given a diagnosis of probable CTE at that time, based on clinical symptoms and history, Gandy said. He subsequently heard about tau imaging work being done by Gandy's group and volunteered to be evaluated there.
His chief complaints were emotional disturbance and cognitive decline. Although he performed very well on several domains of neuropsychological testing, Gandy said, there were declines over time in executive function, processing speed, and motor speed, and his scores on the Boston Naming test were below average. An MRI also revealed diffuse atrophy, especially in the frontal lobe, basal ganglia, and lateral temporal lobe, all of which are key elements of CTE.
Tau imaging revealed deposition in the bilateral cingulate, occipital, and orbitofrontal cortices, as well as several temporal areas. But the hallmark of CTE -- what distinguishes it from Alzheimer's and other tauopathies -- was the deposition of tau in cortical gray matter/white matter junctions, Gandy said.
"When tangles follow the wrinkles of the brain, near the surface, that occurs in CTE and only CTE," Gandy said.
Indeed, that was the conclusion of an , charged with defining the neuropathological criteria for the diagnosis of CTE. Experts hope that this definition will supplant the need for post-mortem confirmation of the disease.
Getting post-mortem confirmation is much easier in conditions like Alzheimer's, which predominantly affects older patients. CTE patients could live for decades, which would make getting a diagnosis on autopsy difficult.
Whether requirements for post-mortem confirmation of CTE will be lifted remains to be seen. Gandy said his group has imaged about 20 concussion patients so far, and four of them have probable CTE based on clinical symptoms. Of those four, three had positive tau scans.
"Only one patient with clinical CTE had a negative scan," Gandy said. "The others were concussed, but they didn't have clinical CTE. We didn't know what sort of injury would be required to see any signal, so we scanned a lot of patients."
As to why the one clinical CTE patient didn't have a positive tau scan: "We don't know the natural history. We don't know if the image may change over time. Perhaps the [tau] tangles come and go."
Last year, another research group led by , of NorthShore University Health System in Evanston, Ill., and colleagues found that a different tracer [18F]FDDNP detected tau buildup in relevant areas of the brains of 14 retired NFL players who'd had concussions, and these areas were different from tau scans in Alzheimer's patients.
But Gandy's group noted that Bailes and colleagues didn't do amyloid scanning with florbetapir to further rule out Alzheimer's, as the tracer they used could bind to amyloid as well as tau. On the other hand, AV1451 is highly selective and specific for tau, and their team did do amyloid scans to rule out Alzheimer's, they pointed out.
The next step for Gandy's group is to conduct a trial of taxanes in patients who've had CTE confirmed on tau imaging. Gandy said the drugs have shown promise in animal models of the disease. Members of this drug class include paclitaxel (Abraxane) and docetaxel (Taxotere).
Disclosures
The study was supported by the Alzheimer's Drug Discovery Foundation, the NINDS, NICHD, Avid Radiopharmaceutical, Eli Lilly, and the Werber Family Foundation.
Avid Radiopharmaceutical donated the radiotracer.
Gandy and co-authors disclosed no relevant relationships with industry.
Primary Source
Translational Psychiatry
Dickstein DL, et al "Cerebral [18F]T807/AV1451 retention pattern in clinically probably CTE resembles pathognomonic distribution of CTE tauopathy" Trans Psych 2016; DOI: 10.1038/tp.2016.175.