White Matter Integrity Involvement in the Preclinical Stage of Familial Creutzfeldt–Jakob Disease: A Diffusion Tensor Imaging Study

Jing, Donglai; Chen, Yaojing; Xie, Kexin; Cui, Yue; Cui, Chunlei; Liu, Li; Lu, Hui; Ye, Jing; Gao, Ran; Wang, Lin; Liang, Zhigang; Zhang, Zhanjun; Wu, Liyong

doi:10.3389/fnagi.2021.655667

Cited by 2 publications

(1 citation statement)

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“…In this study, we conducted the longitudinal assessment of glucose metabolism using FDG-PET in asymptomatic PRNP mutation carriers, to explore their vulnerable brain regions and changing trajectories. All PRNP mutation carriers were from the same pedigree which had been reported in our previous work [12][13][14]. To put our preclinical gCJD research into the context of general gCJD, we also enrolled affected gCJD patients as well as normal controls.…”

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confidence: 99%

A longitudinal 18F-FDG PET/MRI study in asymptomatic stage of genetic Creutzfeldt–Jakob disease linked to G114V mutation

et al. 2022

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Background Pathogenic prion protein may start to deposit in some brain regions and cause functional alterations in the asymptomatic stage in Creutzfeldt–Jakob disease. The study aims to determine the trajectory of the brain metabolic changes for prion protein diseases at the preclinical stage. Methods At baseline, we enrolled five asymptomatic PRNP G114V mutation carriers, six affected genetic PRNP E200K CJD patients and 23 normal controls. All participants completed clinical, diffusion-weighted imaging (DWI) and 18F fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) examinations. Longitudinal follow-up was completed in five asymptomatic mutation carriers. We set three-time points to identify the changing trajectory in the asymptomatic carriers group including baseline, 2-year and 4-year follow-up. Results At baseline, DWI signals, the cerebral glucose standardized uptake value rate ratio (SUVR) and clinical status in 5 asymptomatic cases were normal. At the follow-up period, mild hypometabolism on PET images was found in asymptomatic carriers without any DWI abnormal signal. Further group quantitatively analysis showed hypometabolic brain regions in the asymptomatic genetic CJD group were in the insula, frontal, parietal, and temporal lobes in 4-year follow-up. The SUVR changing trajectories of all asymptomatic cases were within the range between the normal controls and affected patients. Notably, the SUVR of one asymptomatic individual whose baseline age was older showed a rapid decline at the last follow-up. Conclusions Our study illustrates that the neurodegenerative process associated with genetic CJD may initiate before the clinical presentation of the disease.

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Section: Introductionmentioning

confidence: 99%

A longitudinal 18F-FDG PET/MRI study in asymptomatic stage of genetic Creutzfeldt–Jakob disease linked to G114V mutation

et al. 2022

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Prion Mutations in Republic of Republic of Korea, China, and Japan

Kim

Shim

Bagyinszky

et al. 2022

IJMS

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Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt–Jakob Disease (CJD), Gerstmann–Sträussler–Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer’s disease, dementia with Lewy bodies, Parkinson’s disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail. Several prion mutations are specific to Asians and have rarely been reported in countries outside Asia. For example, PRNP V180I and M232R, which are rare in other countries, are frequently detected in Republic of Korea and Japan. PRNP T188K is common in China, and E200K is significantly more common among Libyan Jews in Israel. The A117V mutation has not been detected in any Asian population, although it is commonly reported among European GSS patients. In addition, V210I or octapeptide insertion is common among European CJD patients, but relatively rare among Asian patients. The reason for these differences may be geographical or ethical isolation. In terms of clinical phenotypes, V180I, P102L, and E200K present diverse clinical symptoms with disease duration, which could be due to other genetic and environmental influences. For example, rs189305274 in the ACO1 gene may be associated with neuroprotective effects in cases of V180I mutation, leading to longer disease survival. Additional neuroprotective variants may be possible in cases featuring the E200K mutation, such as KLKB1, KARS, NRXN2, LAMA3, or CYP4X1. E219K has been suggested to modify the disease course in cases featuring the P102L mutation, as it may result in the absence of prion protein-positive plaques in tissue stained with Congo red. However, these studies analyzed only a few patients and may be too preliminary. The findings need to be verified in studies with larger sample sizes or in other populations. It would be interesting to probe additional genetic factors that cause disease progression or act as neuroprotective factors. Further studies are needed on genetic modifiers working with prions and alterations from mutations.

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White Matter Integrity Involvement in the Preclinical Stage of Familial Creutzfeldt–Jakob Disease: A Diffusion Tensor Imaging Study

Cited by 2 publications

References 21 publications

A longitudinal 18F-FDG PET/MRI study in asymptomatic stage of genetic Creutzfeldt–Jakob disease linked to G114V mutation

A longitudinal 18F-FDG PET/MRI study in asymptomatic stage of genetic Creutzfeldt–Jakob disease linked to G114V mutation

Prion Mutations in Republic of Republic of Korea, China, and Japan

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