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BMC neurology, 2019. 19(1), 211-, DOI: https://doi.org/10.1186/s12883-019-1434-z
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 and Sang Won Seo
Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse offtargetbindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamineoxidase 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 asporadic 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, visualdisturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporoparieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parietooccipitalregions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weaklypositive for 14–3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive declinealong with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivityfor 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 mightbe caused by an off-target binding driven by its high affinity for MAO-B.
- DOI: https://doi.org/10.1186/s12883-019-1434-z
- ISBN or ISSN: 1471-2377
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.