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

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 
Citation
 BMC NEUROLOGY, Vol.19(1) : 211, 2019 
Journal Title
 BMC NEUROLOGY 
Issue Date
2019
MeSH
Aged ; Aminopyridines/pharmacology* ; Autopsy ; Brain/diagnostic imaging ; Brain/pathology ; Carbolines/pharmacology* ; Creutzfeldt-Jakob Syndrome/diagnostic imaging* ; Creutzfeldt-Jakob Syndrome/pathology* ; Humans ; Male ; Monoamine Oxidase/metabolism ; Neurofibrillary Tangles/pathology ; Positron-Emission Tomography/methods* ; Quinolines/pharmacology* ; tau Proteins/metabolism
Keywords
Creutzfeldt-Jakob disease ; Flortaucipir PET ; Monoamine oxidase B ; THK5351 PET
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.
Files in This Item:
T201904454.pdf Download
DOI
10.1186/s12883-019-1434-z
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
Ryu, Young Hoon(유영훈) ORCID logo https://orcid.org/0000-0002-9000-5563
Cho, Hanna(조한나) ORCID logo https://orcid.org/0000-0001-5936-1546
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173303
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