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

Abstract

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.

Sports-related brain injuries: connecting pathology to diagnosis

“…129 The study of the 5 players by Small et al 129 was followed by a larger study involving 18 F-FDDNP PET imaging of 14 retired professional football players (5 of whom were included in the earlier study) with suspected CTE and 24 patients with Alzheimer's dementia. 7 In vivo imaging suggests that tau deposition in the football player group was consistent with the postmortem pattern of confirmed CTE cases previously described by McKee et al and Omalu et al Both methods showed involvement of subcortical structures, the medial temporal lobe, and the frontal cortex. In addition, the FDDNP signal in the suspected CTE group was distinct from that of the AD group, which suggests that this tracer can be specific for CTE.…”

An investigation of neuroinjury biomarkers after sport-related concussion: from the subacute phase to clinical recovery

“…The discrepancy between the current studies' findings and those of Nesilus and colleagues are unclear, warranting future research on the potential dysregulation of plasma T-tau chronically after brain injury. Understanding the relationship between peripheral blood T-tau levels and axonal injury or the accumulation of tau in the brain is important, as peripheral tau has been linked to chronic neurodegenerative disorders such as chronic traumatic encephalopathy and Alzheimer's disease (42,47,(50)(51)(52)(53)(54).…”

Progressive Focal Gray Matter Volume Loss in a Former High School Football Player: A Possible Magnetic Resonance Imaging Volumetric Signature for Chronic Traumatic Encephalopathy

“…Imaging has been a particularly powerful application, with positron emission tomography (PET) scans using 2-(1-{6-[ (2-[F-18] fluoroethyl) (methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) revealing high signals in the brainstem, amygdala, and orbital frontal cortex. 7,8 These same brain region show high tau accumulation in autopsy cases of CTE. Diffusion tensor imaging has also suggested abnormalities in fractional anisotropy in patients with depression and anxiety after TBI.…”