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

Hee Jin Kim, Hanna Cho, Seongbeom Park, Hyemin Jang, Young Hoon Ryu, Jae Yong Choi, Seung Hwan Moon, Seung Jun Oh, Minyoung Oh, Duk L. Na, Chul Hyoung Lyoo, Eun Joo Kim, William W. Seeley, Jae Seung Kim, Kyung Chan Choi, Sang Won Seo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number211
JournalBMC neurology
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 Aug 29

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Kim, H. J., Cho, H., Park, S., Jang, H., Ryu, Y. H., Choi, J. Y., Moon, S. H., Oh, S. J., Oh, M., Na, D. L., Lyoo, C. H., Kim, E. J., Seeley, W. W., Kim, J. S., Choi, K. C., & Seo, S. W. (2019). THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: A case report. BMC neurology, 19(1), [211]. https://doi.org/10.1186/s12883-019-1434-z