Dataset Information

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

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.

SUBMITTER: Kim HJ

PROVIDER: S-EPMC6714095 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Kim Hee Jin HJ Cho Hanna H Park Seongbeom S Jang Hyemin H Ryu Young Hoon YH Choi Jae Yong JY Moon Seung Hwan SH Oh Seung Jun SJ Oh Minyoung M Na Duk L DL Lyoo Chul Hyoung CH Kim Eun-Joo EJ Seeley William W WW Kim Jae Seung JS Choi Kyung Chan KC Seo Sang Won SW

BMC neurology 20190829 1

<h4>Background</h4>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 ...[more]

PMID: 31464590

Similar Datasets

Project description:The familial or genetic Creutzfeldt-Jakob disease (fCJD or gCJD) is the inherent form of human prion diseases, which accounts for approximately 10-15% of human prion diseases that are caused by mutations of the prion protein gene (PRNP). In this study, the global expression patterns of the parietal cortex from a patient with G114V gCJD were comparatively analyzed with the normal controls by using a commercial human genome expression chip. Totally 8774 genes showed differential expression, among them 2769 genes were upregulated and 6005 ones were downregulated. The reliability of the results was confirmed by the real-time RT-PCR assays for several specific genes. The most differentially expressed genes involved in the functions of regulation of transcription, ion transport, transcription, cell adhesion, signal transduction. The gene associated with gliosis was upregulated and the genes marked for neurons were downregulated, while the transcription of PRNP gene maintained unchanged. 169 different pathways showed significantly changed in the brain of G114V gCJD. The most significantly regulated pathways included that of Alzheimer’s and Parkinson’s disease, oxidative phosphorylation, regulation of actin cytoskeleton, MAPK signaling pathway and proteasome, which were described in prion diseases previously. In addition, some rarely addressed pathways in prion diseases, such as axon guidance, gap junction and purine metabolism, were also significantly changed in G114V gCJD. The transcriptional situations of the most genes in the top ten changed pathways were down-regulated. The extensive reductions of gene expressions in G114V gCJD showed the comparable profiles with sporadic CJD. The data here raised the useful clues for understanding the pathogenesis of the disease and selecting the potential biomarkers for diagnostic and therapeutic tools. Brain tissues of parietal cortex from a definitely diagnosed G114V gCJD were enrolled into this study. The patient was a 47-year-old Han-Chinese woman at the onset. Neuropathological assays of ten different brain regions revealed typical sCJD-like abnormality and PrPSc deposits. Meanwhile, a commercial normal human parietal cortex total RNA (Clontech) pooled from four male/female aged 35-89 was utilized as control.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets