Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy

Lesman‐Segev, Orit H.; Joie, Renaud La; Stephens, Melanie; Sonni, Ida; Tsai, Richard; Bourakova, Viktoriya; Visani, Adrienne; Edwards, Lauren; O’Neil, James P.; Baker, Suzanne L.; Gardner, Raquel C.; Janabi, Mustafa; Chaudhary, Kiran; Perry, David C.; Kramer, Joel H.; Miller, Bruce L.; Jagust, William J.; Rabinovici, Gil D.

doi:10.1016/j.nicl.2019.102025

Cited by 56 publications

(77 citation statements)

References 73 publications

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“…This pattern was clearly shown in this individual using a new tau tracer 18 F-MK6240. This pattern of tau tracer distribution has been reported in group-level analyses of symptomatic retired NFL players imaged with Flortaucipir ( 16 , 17 ) and a case report of a retired NFL player with CTE confirmed by neuropathological examination ( 18 ). However, quantitative tau results were within the range of control participants in the case–control studies, and limited antemortem–postmortem correlation was observed in the case study.…”

Section: Discussionsupporting

confidence: 68%

“…Recently, a study using the tau tracer 18 F-AV1451 (Flortaucipir) identified higher tracer retention in bilateral superior frontal, bilateral medial temporal, and left parietal regions in retired National Football League (NFL) players relative to controls, in grouplevel analyses (16). This frontotemporal pattern has also been reported in another group-level analysis of retired NFL players (17), but neither study had neuropathological confirmation of CTE. In both studies, the pattern was not a consistent feature at an individual level and the quantitative results overlapped with the control range.…”

Section: Introductionmentioning

confidence: 93%

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Case Report: 18F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player

et al. 2020

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Introduction: It remains unclear if tau imaging may assist diagnosis of chronic traumatic encephalopathy (CTE). Flortaucipir PET has shown superior frontal with medial temporal tau binding consistent with the provisional neuropathological criteria for mid-stage CTE in group-level analyses of retired symptomatic NFL players and in one individual with pathologically confirmed CTE. 18F-MK6240 is a new PET ligand that has high affinity for tau. We present the case of a 63-year-old cognitively impaired, former Australian rules football player with distinct superior frontal and medial temporal 18F-MK6240 binding and show it to be significantly different to the pattern seen in prodromal Alzheimer's disease (AD).Findings: The participant was recruited for a study of amyloid-β and tau several decades after traumatic brain injury. He had multiple concussions during his football career but no cognitive complaints at retirement. A thalamic stroke in his mid 50s left stable mild cognitive deficits but family members reported further short-term memory, behavioral, and personality decline preceding the study. Imaging showed extensive small vessel disease on MRI, a moderate burden of amyloid-β plaques, and 18F-MK6240 binding in bilateral superior frontal and medial temporal cortices. Voxel-wise analysis demonstrated that the frontally predominant pattern of the participant was significantly different to the posterior temporo-parietal predominant pattern of prodromal AD.Conclusion: Although lacking neuropathological examination to distinguish CTE from a variant of AD, the clear demonstration of a CTE-like tau pattern in a single at-risk individual suggests further research on the potential of 18F-MK6240 PET for identifying CTE is warranted.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 93%

Case Report: 18F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player

et al. 2020

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“…For CTE, there is a modest correlation between Tauvid PET results and postmortem pathology [ 53 ]. Various studies have shown some potential of Tauvid for CTE but it still has its limitations [ 53 , 54 , 55 , 56 ]. Further studies with second-generation tracers might elucidate the use of tau PET imaging in CTE and other tau-related neurodegenerative diseases.…”

Section: Perspectivementioning

confidence: 99%

Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

et al. 2021

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Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.

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“…Younger people may experience more behavioural and/or mood symptoms with older persons exhibiting cognitive and motor impairment similar to dementia (Davis et al, 2015;Huber et al, 2016;Bailes et al, 2015;Bieniek et al, 2015;Stern et al, 2013). The causes of CTE vary by study with some stating that a single blunt force episode may be sufficient (Omalu et al, 2011) with others stating that CTE develops following repetitive concussive or sub-concussive events (Armstrong et al, 2016;Omalu et al, 2010;Edwards et al, 2017;Huber et al, 2016;Lesman-Segeva et al, 2019;McKee, Abdolmohammadi et al, 2018;Stern et al, 2011;Tsai, 2020;VanItallie, 2019) or both (Bailes et al, 2019). Limited prevalence data suggest that CTE has been observed in 9% of autopsy cases with a history sport participation versus 3% of those with no history of participation in sport (Bieniek et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Understanding Post-Career adjustment in Ex-Professional Ice Hockey Enforcers: Concussion history and chronic pain

Gaetz

2021

Cogent Medicine

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Tau PET and multimodal brain imaging in patients at risk for chronic traumatic encephalopathy

Abstract: HighlightsElevated tau PET signal was seen in a subset of patients at risk for CTE.Highest tracer retention was found in patients with positive amyloid PET.Tau PET, FDG and MRI showed converging abnormalities in frontotemporal regions.

Cited by 56 publications

References 73 publications

Case Report: 18F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player

Case Report: 18F-MK6240 Tau Positron Emission Tomography Pattern Resembling Chronic Traumatic Encephalopathy in a Retired Australian Rules Football Player

Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

Understanding Post-Career adjustment in Ex-Professional Ice Hockey Enforcers: Concussion history and chronic pain

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