scholarly journals A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis

2020 ◽  
Author(s):  
Penny J. Norsworthy ◽  
Andrew G.B. Thompson ◽  
Tze H. Mok ◽  
Fernando Guntoro ◽  
Luke C. Dabin ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Prion Diseases ◽  
Disease Diagnosis ◽  
Small Rna Sequencing ◽  
Mirna Signature ◽  
Progressive Dementia ◽  
Cross Sectional ◽  
Molecular Alterations ◽  
Mrna Targets ◽  
Jakob Disease

AbstractSporadic Creutzfeldt-Jakob disease (sCJD) presents as a rapidly progressive dementia which is usually fatal within six months. No clinical blood tests are currently available for diagnosis or disease monitoring. Here, we profiled blood microRNA (miRNA) expression in sCJD. Small RNA-sequencing of 57 sCJD patients and 48 healthy controls revealed differential expression of hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-93-5p and hsa-miR-106b-3p. Downregulation of hsa-let-7i-5p, hsa-miR-16-5p and hsa-miR-93-5p replicated in an independent cohort using quantitative PCR, with concomitant upregulation of four of their mRNA targets. Absence of correlation in cross-sectional analysis with clinical phenotypes paralleled the lack of association between rate of decline in miRNA expression and rate of disease progression in a longitudinal cohort of 50 samples from 21 sCJD patients. Finally, the miRNA signature showed a high level of accuracy in discriminating sCJD from Alzheimer’s disease (AD). These findings highlight novel molecular alterations in the periphery in sCJD which can provide information about differential diagnosis and improve mechanistic understanding of human prion diseases.

scholarly journals RNA editing alterations define manifestation of prion diseases

2019 ◽  
Vol 116 (39) ◽  
pp. 19727-19735 ◽  
Author(s):  
Eirini Kanata ◽  
Franc Llorens ◽  
Dimitra Dafou ◽  
Athanasios Dimitriadis ◽  
Katrin Thüne ◽  
...  
Keyword(s):  
Disease Progression ◽  
Rna Editing ◽  
Prion Disease ◽  
Prion Diseases ◽  
Rapid Progression ◽  
Human Prion Disease ◽  
Progressive Dementia ◽  
Molecular Alterations ◽  
Jakob Disease ◽  
Subtype A

Prion diseases are fatal neurodegenerative disorders caused by misfolding of the normal prion protein into an infectious cellular pathogen. Clinically characterized by rapidly progressive dementia and accounting for 85% of human prion disease cases, sporadic Creutzfeldt–Jakob disease (sCJD) is the prevalent human prion disease. Although sCJD neuropathological hallmarks are well-known, associated molecular alterations are elusive due to rapid progression and absence of preclinical stages. To investigate transcriptome alterations during disease progression, we utilized tg340-PRNP129MM mice infected with postmortem material from sCJD patients of the most susceptible genotype (MM1 subtype), a sCJD model that faithfully recapitulates the molecular and pathological alterations of the human disease. Here we report that transcriptomic analyses from brain cortex in the context of disease progression, reveal epitranscriptomic alterations (specifically altered RNA edited pathway profiles, eg., ER stress, lysosome) that are characteristic and possibly protective mainly for preclinical and clinical disease stages. Our results implicate regulatory epitranscriptomic mechanisms in prion disease neuropathogenesis, whereby RNA-editing targets in a humanized sCJD mouse model were confirmed in pathological human autopsy material.

Demencia rápidamente progresiva, sobre el reporte de un caso de Creutzfeldt-Jakob

2020 ◽  
Vol 63 (6) ◽  
pp. 31-37
Author(s):  
Osvaldo Iván Guevara Valmaña ◽  
Juan Pablo Venzor Castellano ◽  
Angélica Martínez Jiménez
Keyword(s):  
Short Term Memory ◽  
Prion Diseases ◽  
Emotional Lability ◽  
Short Term ◽  
Progressive Dementia ◽  
Memory Disorder ◽  
Jakob Disease ◽  
Depressive Episodes ◽  
Positive Results ◽  
Current Standards

The Creutzfeldt-Jakob disease is a neurodegenerative, neuroselective and fatal entity, that is not usually reported in Mexico. We present a 40-year-old male patient who presents the onset of this illness, with short-term memory disorder, depressive episodes and emotional lability with a tendency to irritability. He also presents space disorientation, decreased strength of the left and lateral hemibody drive in the ipsilateral walk, and insomnia, for which he is admitted to the hospital during 40 days for diagnostic approach. Several studies were carried out during his hospital stay, the most relevant for the diagnosis: a magnetic resonance which presented ""cortical ribboning"" and hyperintensities in the nuclei of the base, both diagnosis highly suggested the pathology. The positive results to protein 14-3-3 reaffirmed the diagnosis. After 15 months of the onset of neurological symptoms, the patient presented symptoms of pneumonia, which lead to the hospitalization. During his stay, he presented a pulmonary abscess and rapid progressive dementia. The patient died in the hospital by a pulmonary sepsis 18 months after the onset of symptoms. No necropsy was performed, following the current standards for the disease management. Keywords: Creutzfeldt-Jakob disease; prion diseases; rapidly progressive dementia.

scholarly journals PMCA Applications for Prion Detection in Peripheral Tissues of Patients with Variant Creutzfeldt-Jakob Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 405 ◽  
Author(s):  
Giorgio Giaccone ◽  
Fabio Moda
Keyword(s):  
Protein Misfolding ◽  
Prion Diseases ◽  
Disease Diagnosis ◽  
Diagnostic Techniques ◽  
Spongiform Encephalopathy ◽  
Variant Form ◽  
Definite Diagnosis ◽  
Peripheral Tissues ◽  
New Variant ◽  
Jakob Disease

Prion diseases are neurodegenerative and invariably fatal conditions that affect humans and animals. In particular, Creutzfeldt-Jakob disease (CJD) and bovine spongiform encephalopathy (BSE) are paradigmatic forms of human and animal prion diseases, respectively. Human exposure to BSE through contaminated food caused the appearance of the new variant form of CJD (vCJD). These diseases are caused by an abnormal prion protein named PrPSc (or prion), which accumulates in the brain and leads to the onset of the disease. Their definite diagnosis can be formulated only at post-mortem after biochemical and neuropathological identification of PrPSc. Thanks to the advent of an innovative technique named protein misfolding cyclic amplification (PMCA), traces of PrPSc, undetectable with the standard diagnostic techniques, were found in peripheral tissues of patients with vCJD, even at preclinical stages. The technology is currently being used in specialized laboratories and can be exploited for helping physicians in formulating an early and definite diagnosis of vCJD using peripheral tissues. However, this assay is currently unable to detect prions associated with the sporadic CJD (sCJD) forms, which are more frequent than vCJD. This review will focus on the most recent advances and applications of PMCA in the field of vCJD and other human prion disease diagnosis.

scholarly journals Cardiac miRNA Expression and their mRNA Targets in a Rat Model of Prediabetes

2020 ◽  
Vol 21 (6) ◽  
pp. 2128
Author(s):  
Éva Sághy ◽  
Imre Vörös ◽  
Bence Ágg ◽  
Bernadett Kiss ◽  
Gábor Koncsos ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Mirna Expression ◽  
Drug Targets ◽  
Zinc Finger Protein ◽  
Target Prediction ◽  
Mirna Expression Profile ◽  
Differentially Expressed ◽  
Small Rna Sequencing ◽  
Mrna Targets ◽  
Differentially Expressed Mirnas

Little is known about the mechanism of prediabetes-induced cardiac dysfunction. Therefore, we aimed to explore key molecular changes with transcriptomic and bioinformatics approaches in a prediabetes model showing heart failure with preserved ejection fraction phenotype. To induce prediabetes, Long-Evans rats were fed a high-fat diet for 21 weeks and treated with a single low-dose streptozotocin at week 4. Small RNA-sequencing, in silico microRNA (miRNA)-mRNA target prediction, Gene Ontology analysis, and target validation with qRT-PCR were performed in left ventricle samples. From the miRBase-annotated 752 mature miRNA sequences expression of 356 miRNAs was detectable. We identified two upregulated and three downregulated miRNAs in the prediabetic group. We predicted 445 mRNA targets of the five differentially expressed miRNAs and selected 11 mRNAs targeted by three differentially expressed miRNAs, out of which five mRNAs were selected for validation. Out of these five targets, downregulation of three mRNAs i.e., Juxtaposed with another zinc finger protein 1 (Jazf1); RAP2C, member of RAS oncogene family (Rap2c); and Zinc finger with KRAB and SCAN domains 1 (Zkscan1) were validated. This is the first demonstration that prediabetes alters cardiac miRNA expression profile. Predicted targets of differentially expressed miRNAs include Jazf1, Zkscan1, and Rap2c mRNAs. These transcriptomic changes may contribute to the diastolic dysfunction and may serve as drug targets.

scholarly journals Creutzfeldt-Jakob Disease Presenting as Expressive Aphasia and Nonconvulsive Status Epilepticus

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Hafiz B. Mahboob ◽  
Kazi H. Kaokaf ◽  
Jeremy M. Gonda
Keyword(s):  
Status Epilepticus ◽  
Clinical Presentation ◽  
Prion Diseases ◽  
Epileptiform Activity ◽  
Rare Condition ◽  
Nonconvulsive Status Epilepticus ◽  
Mri Findings ◽  
Progressive Dementia ◽  
Csf Analysis ◽  
Jakob Disease

Creutzfeldt-Jakob disease (CJD), the most common form of human prion diseases, is a fatal condition with a mortality rate reaching 85% within one year of clinical presentation. CJD is characterized by rapidly progressive neurological deterioration in combination with typical electroencephalography (EEG) and magnetic resonance imaging (MRI) findings and positive cerebrospinal spinal fluid (CSF) analysis for 14-3-3 proteins. Unfortunately, CJD can have atypical clinical and radiological presentation in approximately 10% of cases, thus making the diagnosis often challenging. We report a rare clinical presentation of sporadic CJD (sCJD) with combination of both expressive aphasia and nonconvulsive status epilepticus. This patient presented with slurred speech, confusion, myoclonus, headaches, and vertigo and succumbed to his disease within ten weeks of initial onset of his symptoms. He had a normal initial diagnostic workup, but subsequent workup initiated due to persistent clinical deterioration revealed CJD with typical MRI, EEG, and CSF findings. Other causes of rapidly progressive dementia and encephalopathy were ruled out. Though a rare condition, we recommend consideration of CJD on patients with expressive aphasia, progressive unexplained neurocognitive decline, and refractory epileptiform activity seen on EEG. Frequent reimaging (MRI, video EEGs) and CSF examination might help diagnose this fatal condition earlier.

Brains with sporadic Creutzfeldt-Jakob disease and copathology showed a prolonged end-stage of disease

2017 ◽  
Vol 71 (5) ◽  
pp. 446-450 ◽  
Author(s):  
Aitzol Miguelez-Rodriguez ◽  
Jorge Santos-Juanes ◽  
Ikerne Vicente-Etxenausia ◽  
Katty Perez de Heredia-Goñi ◽  
Beatriz Garcia ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Prion Diseases ◽  
Prognostic Significance ◽  
Alpha Synuclein ◽  
Phosphorylated Tau ◽  
Progressive Dementia ◽  
Associated Proteins ◽  
Jakob Disease ◽  
End Stage ◽  
Univariate Analyses

AimsTo investigate the expression of major proteins related to primary neurodegenerative diseases and their prognostic significance in brains with Creutzfeldt-Jakob disease (CJD).Materials and methodsThirty consecutive cases of confirmed CJD during the period 2010–2015 at Basque Brain bank were retrospectively reviewed. Moreover, major neurodegenerative-associated proteins (phosphorylated Tau, 4R tau, 3R tau, alpha-synuclein, TDP43, amyloid beta) were tested. Clinical data were reviewed. Cases were divided according to the presence or absence of copathology. Survival curves were also determined.ResultsCopathology was significantly associated with survival in brains with CJD (4.2±1.2 vs 9.2±1.9; P=0.019) and in brains with MM1/MV1 CJD (2.1±1.0 vs 6.7±2.8; P=0.012). Besides, the presence of more than one major neurodegenerative-associated protein was significantly associated with survival (4.2±1.2 vs 10.7±2.6; P=0.017). Thus, univariate analyses further pointed out variables significantly associated with better survival: copathology in CJD (HR=0.430; P=0.033); more than one neurodegenerative-associated protein in CJD (HR=0.369; P=0.036) and copathology in MM1/MV1 CJD (HR=0.525; P=0.032).ConclusionThe existence of copathology significantly prolongs survival in patients with rapidly progressive dementia due to CJD. The study of major neurodegenerative-associated proteins in brains with CJD could allow us to further understand the molecular mechanisms behind prion diseases.

scholarly journals A blood miRNA signature associates with sporadic Creutzfeldt-Jakob disease diagnosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Penny J. Norsworthy ◽  
Andrew G. B. Thompson ◽  
Tze H. Mok ◽  
Fernando Guntoro ◽  
Luke C. Dabin ◽  
...  
Keyword(s):  
Disease Diagnosis ◽  
Mirna Signature ◽  
Jakob Disease

Cellular factors important for the de novo formation of yeast prions

2008 ◽  
Vol 36 (5) ◽  
pp. 1083-1087 ◽  
Author(s):  
Mick Tuite ◽  
Klement Stojanovski ◽  
Frederique Ness ◽  
Gloria Merritt ◽  
Nadejda Koloteva-Levine
Keyword(s):  
De Novo ◽  
Prion Diseases ◽  
Underlying Mechanism ◽  
Structural Form ◽  
Yeast Saccharomyces Cerevisiae ◽  
Yeast Prions ◽  
Cellular Factors ◽  
Jakob Disease ◽  
Protein Rich ◽  
Cis And Trans

Prions represent an unusual structural form of a protein that is ‘infectious’. In mammals, prions are associated with fatal neurodegenerative diseases such as CJD (Creutzfeldt–Jakob disease), while in fungi they act as novel epigenetic regulators of phenotype. Even though most of the human prion diseases arise spontaneously, we still know remarkably little about how infectious prions form de novo. The [PSI+] prion of the yeast Saccharomyces cerevisiae provides a highly tractable model in which to explore the underlying mechanism of de novo prion formation, in particular identifying key cis- and trans-acting factors. Most significantly, the de novo formation of [PSI+] requires the presence of a second prion called [PIN+], which is typically the prion form of Rnq1p, a protein rich in glutamine and aspartic acid residues. The molecular mechanism by which the [PIN+] prion facilitates de novo [PSI+] formation is not fully established, but most probably involves some form of cross-seeding. A number of other cellular factors, in particular chaperones of the Hsp70 (heat-shock protein 70) family, are known to modify the frequency of de novo prion formation in yeast.

scholarly journals A Case of Familial Creutzfeldt-Jakob Disease Presenting with Dry Cough

2006 ◽  
Vol 33 (2) ◽  
pp. 243-245 ◽  
Author(s):  
Sandrine Larue ◽  
Steve Verreault ◽  
Peter Gould ◽  
Michael B. Coulthart ◽  
Catherine Bergeron ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Mutation Screening ◽  
Disease Onset ◽  
Visual Hallucinations ◽  
Progressive Dementia ◽  
Gene Encoding ◽  
Progressive Ataxia ◽  
Persistent Cough ◽  
Jakob Disease ◽  
Classical Triad

ABSTRACT:Background:Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) is based on the classical triad of rapidly progressive dementia, myoclonus and abnormal EEG. The 200k mutation within the gene encoding PrP, located on the short arm of chromosome 20, accounts for more than 70% of families with CJD worldwide.Case Report:Herein, we report a patient who developed persistent dry cough and classical signs of CJD, including severe cognitive decline, cerebellar signs, and myoclonic jerks, leading to death a few weeks after disease onset. Mutation screening showed that he had the 200k point mutation in the PRNP gene. His mother had died twenty years earlier with neuropathologically confirmed CJD. She had presented a rapidly progressive ataxia with myoclonus, dementia, visual hallucinations, and the same persistent dry cough.Conclusions:The clinical presentation of this familial CJD case with persistent dry cough is quite unusual. Therefore, a neurological etiology should be sought when confronted with an unexplained persistent cough.

Heidenhain variant of Creutzfeldt–Jakob disease diagnosis: Place of MRI

2010 ◽  
Vol 75 (2) ◽  
pp. e47-e50
Author(s):  
Gabrielle Weber-Donat ◽  
Elsa Ukkola-Pons ◽  
Nicolas Donat ◽  
Cyril Garcia ◽  
Christophe Teriitehau ◽  
...  
Keyword(s):  
Disease Diagnosis ◽  
Jakob Disease
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