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THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: a case report.

  • Author(s): 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;
  • Seo, Sang Won
  • et al.
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.

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