1. THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: a case report.
- Author
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Kim, Hee Jin, Cho, Hanna, Park, Seongbeom, Jang, Hyemin, Ryu, Young Hoon, Choi, Jae Yong, Moon, Seung Hwan, Oh, Seung Jun, Oh, Minyoung, Na, Duk L., Lyoo, Chul Hyoung, Kim, Eun-Joo, Seeley, William W., Kim, Jae Seung, Choi, Kyung Chan, and Seo, Sang Won
- Subjects
CREUTZFELDT-Jakob disease ,CEREBROSPINAL fluid examination ,BOVINE spongiform encephalopathy ,MONOAMINE oxidase ,MYOCLONUS ,NEUROFIBRILLARY tangles - Abstract
Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study.Case Presentation: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrPsc, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody.Conclusions: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B. [ABSTRACT FROM AUTHOR]- Published
- 2019
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