In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging

• Published in: Proceedings of the National Academy of Sciences - PNAS 2015-04, Vol.112 (16), p.E2039-E2047
• Main Authors: Barrio, Jorge R., Small, Gary W., Wong, Koon-Pong, Huang, Sung-Cheng, Liu, Jie, 刘捷, Merrill, David A., Giza, Christopher C., Fitzsimmons, Robert P., Omalu, Bennet, Bailes, Julian, Kepe, Vladimir
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Amygdala - microbiology; Amygdala - pathology; Athletes; Autopsy; Behavior; Biological Sciences; Brain - diagnostic imaging; Brain - pathology; Brain diseases; Brain Injury, Chronic - diagnostic imaging; Case-Control Studies; Demography; Emotions; Football; Humans; Male; Medical imaging; Mesencephalon - microbiology; Mesencephalon - pathology; Middle Aged; Nitriles; PNAS Plus; Positron-Emission Tomography; Traumatic brain injury
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1409952112

Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE ( n = 14) and compared results with those of cognitively intact controls ( n = 28) and patients with Alzheimer’s dementia (AD) ( n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-β] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE. Significance Mild traumatic brain injuries are frequent events in the general population and are associated with a severe neurodegenerative disease, chronic traumatic encephalopathy (CTE). This disease is characterized by abnormal accumulation of protein aggregates, primarily tau proteins, which accumulate in brain areas responsible for mood, fear, stress, and cognition. There is no definitive clinical diagnosis of CTE at the present time, and this new work shows how a tau-sensitive brain imaging agent, [F-18]FDDNP, may be able to detect the disease in living people with varying degrees of symptoms. Early detection would facilitate the most effective management strategies and provide a baseline to measure the effectiveness of treatments.