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

• Main Authors: 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
• Format: Article
• Language: English
• Published: BMC 2019-08-01
• Series: BMC Neurology
• Subjects: THK5351 PET; Flortaucipir PET; Monoamine oxidase B; Creutzfeldt-Jakob disease
• Online Access: http://link.springer.com/article/10.1186/s12883-019-1434-z

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.