Tau Ligand for the Diagnosis of Chronic Traumatic Encephalopathy in Retired CFL Athletes
University Health Network, Centre for Addiction and Mental Health, Toronto Western Hospital, Toronto Western Research Institute, Toronto Rehabilitation Institute, Tanz Centre for Research in Neurodegenerative Diseases
“Chronic traumatic encephalopathy” (CTE) is a slowly progressive neurodegenerative disease with tau pathology that manifests years after concussive or subconcussive events. Clinical CTE cases are described as an evolving constellation of psychiatric, cognitive and motor symptoms but currently, CTE can only be diagnosed at autopsy. Although widespread media attention has spawned a dogma on the delayed effects of multiple concussions in the former professional football players, the frequency of long-term neurodegenerative change remains controversial since not all former professional athletes complain of cognitive or neuropsychiatric symptoms and not all athletes who suffer multiple concussions develop CTE. The lack of an in vivo diagnostic tool has limited both accurate diagnosis and treatment. The recent discovery of PET tracer [F-18]-T807 that can bind to abnormal tau protein in vivo represents an opportunity to investigate the presence of pathological tau in vivo in athletes with symptoms that could represent CTE and allow early diagnosis when interventions might be effective.
We will investigate the PET tracer [F-18]-T807 for detecting tau pathology to differentiate former CFL players with multiple concussions and neuropsychiatric and/or cognitive impairments consistent with CTE from asymptomatic former CFL players, AD patients and normal non-concussed controls.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
Currently, we cannot identify which individuals with multiple concussions have CTE. The ability to diagnose CTE in vivo is the first step in trying to treat this disease. Tau-specific agents could be tried in patients with CTE if we could diagnose tau pathology in vivo. Ideally, the PET tracer [F-18]-T807 will identify patients with CTE at an early stage so that treatment could be initiated before CTE progresses to a stage of irreparable damage. Establishing a clear relationship between tau pathology and the neuropsychiatric and cognitive symptoms typical of CTE would spur treatment trials with tau agents in patients with CTE.
Given the prevalence of concussions and the significant morbidity in some people with repeated concussions, the possibility of developing CTE after multiple concussions has become a major public health concern. A means of detecting CTE in vivo provides an opportunity for improved understanding of the development and progression of tau pathology. We know that neurodegenerative diseases begin long before any symptoms become apparent. Detecting tau in vivo before the development of symptoms and signs of CTE may provide a novel avenue for prevention. The ability to detect CTE in vivo will provide an opportunity to plan for the future and to explore potential treatment options.