Thalamic-insomnia phenotype in E200K Creutzfeldt–Jakob disease: A PET/MRI study

Ye, Hong; Chu, Min Kyung; Chen, Zhongyun; Xie, Kexin; Liu, Li; Nan, Haitian; Cui, Yue; Zhang, Jing; Wang, Lin; Li, Junjie; Wu, Liyong

doi:10.1016/j.nicl.2022.103086

Cited by 1 publication

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References 32 publications

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“…A systematic study of European patients found the most reported initial symptoms were fast-progressing dementia, ataxia (> 80% of cases), followed by myoclonus (> 50%), while pyramidal signs and dystonia were reported in about a third of cases 73 . Insomnia has been reported in some patients with the E200K (~8%) 73 , which is consistent with PET scans indicating thalamic hypometabolism 74,75 . This is in clear contrast to the clinical symptoms associated with sporadic CJD and is reminiscent of FFI, described in more detail below.…”

Section: Genetic Creutzfeldt-jakob Diseasesupporting

confidence: 81%

Cell type-specific translatome analysis of mouse models of three genetic neurodegenerative diseases

Bauer

2023

Linköping University Medical Dissertations

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The burden neurodegenerative diseases place on patients, their loved ones, and the healthcare system is significant, and despite extensive research efforts, there is currently no cure. Since degenerative changes in the brain can begin years before symptoms appear, early intervention is critical. Additionally, neurodegenerative diseases target certain brain regions and neuron types early on. A more comprehensive understanding of the affected cells during the presymptomatic phase is therefore crucial for an effective and targeted intervention. Herein, we isolated, sequenced, and analyzed translatome samples from six neuronal cell types in knock-in mouse models of three monogenic neurodegenerative diseases at a presymptomatic stage: genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Huntington's disease (HD). To obtain the translatome samples, we used RiboTag to immunoprecipitate HA-tagged ribosomes with their translating mRNAs from targeted cell types. We analyzed six cell types across two brain regions: cerebral and cerebellar glutamatergic and GABAergic neurons, and cerebral parvalbumin (PV) and somatostatin (SST)-expressing neurons.In the first paper, we focused our analysis on the prion diseases, gCJD (E200K) and FFI (D178N). Here observed a similar response of SST + neurons, a cell type not previously reported as affected, in both disease models. This was characterized by upregulation of ribosomeassociated genes, and downregulation of cytoskeleton and synapse-associated genes in FFI. Weighted gene co-expression network analysis of SST + neurons pointed towards the downregulation of mTOR inhibition as a potential mechanism underlying the observed gene expression changes.In the second paper, we analyzed a 129S4-HdhQ200 knock-in mouse model of HD. Histological and behavioral assessment revealed pathological changes in the striatum and cerebellum at 9 months and a later, mild behavioral phenotype. Translatome analysis indicated a surprisingly strong response in reportedly resistant glutamatergic neurons of the cerebellum, marked by upregulation of cell cycle regulators Ccnd1 and chromobox protein genes.

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Section: Genetic Creutzfeldt-jakob Diseasesupporting

confidence: 81%

Cell type-specific translatome analysis of mouse models of three genetic neurodegenerative diseases

Bauer

2023

Linköping University Medical Dissertations

View full text Add to dashboard Cite

show abstract

Thalamic-insomnia phenotype in E200K Creutzfeldt–Jakob disease: A PET/MRI study

Cited by 1 publication

References 32 publications

Cell type-specific translatome analysis of mouse models of three genetic neurodegenerative diseases

Cell type-specific translatome analysis of mouse models of three genetic neurodegenerative diseases

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