scholarly journals Markers of A1 astrocytes stratify to molecular sub-types in sporadic Creutzfeldt–Jakob disease brain

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Cathryn L Ugalde ◽  
Victoria Lewis ◽  
Christiane Stehmann ◽  
Catriona A McLean ◽  
Victoria A Lawson ◽  
...  
Keyword(s):  
Functional Properties ◽  
Linear Trend ◽  
Polarization State ◽  
Reactive Astrocytes ◽  
Global Changes ◽  
Strong Linear Correlation ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Mrna Markers ◽  
Codon 129

Abstract Astrocytes are glial cells of the central nervous system that become reactive under conditions of stress. The functional properties of reactive astrocytes depend on their stimulus that induces the upregulation of specific genes. Reactive astrocytes are a neuropathological feature of prion disorders; however, their role in the disease pathogenesis is not well understood. Here, we describe our studies of one polarization state of reactive astrocytes, termed A1 astrocytes, in the frontal cortex region of 35 human sporadic Creutzfeldt–Jakob disease brains encompassing a range of molecular sub-types. Examination of two mRNA markers of A1 astrocytes, C3 and GBP2, revealed a strong linear correlation between the two following their log-normalization (P = 0.0011). Both markers were found upregulated in the sporadic Creutzfeldt–Jakob disease brain compared with age-matched control tissues (P = 0.0029 and 0.0002, for C3log and GBP2log, respectively), and stratifying samples based on codon 129 genotype revealed that C3log is highest in homozygous methionine and lowest in homozygous valine patients, which followed a linear trend (P = 0.027). Upon assessing other disease parameters, a significant positive correlation was found between GBP2log and disease duration (P = 0.031). These findings provide evidence for a divergence in the astrocytic environment amongst patients with sporadic Creutzfeldt–Jakob disease based on molecular sub-type parameters of disease. While more research will be needed to determine the global changes in the genomic profiles and resulting functional properties of reactive astrocytes in disease, considering the evidence demonstrating that A1 astrocytes harbour neurotoxic properties, the changes seen in C3log and GBP2log in the current study may reflect differences in pathogenic mechanisms amongst the sporadic Creutzfeldt–Jakob disease sub-types associated with the A1 polarization state.

scholarly journals Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

2021 ◽  
Vol 22 (4) ◽  
pp. 2099
Author(s):  
Nikol Jankovska ◽  
Tomas Olejar ◽  
Radoslav Matej
Keyword(s):  
Prion Protein ◽  
Fluorescent Microscopy ◽  
Amyloid Β ◽  
Amyloid Β Protein ◽  
Β Protein ◽  
Key Characteristics ◽  
Jakob Disease ◽  
Immunohistochemical Methods ◽  
Confocal Fluorescent Microscopy ◽  
Codon 129

Alzheimer’s disease (AD) and sporadic Creutzfeldt–Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins—amyloid β-protein (Aβ) and prion protein (PrPSc), respectively. To investigate the potential morphological colocalization of Aβ and PrPSc aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrPSc aggregates tended to be, in most cases, located separately, and “compound” plaques were relatively rare. We observed PrPSc plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer’s association guidelines, and prion protein subtype with codon 129 methionine–valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrPSc co-aggregates. However, our data showed that PrPSc aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.

Sporadic Creutzfeldt-Jakob Disease: Diagnosing Typical and Atypical Presentations under Limited Circumstances

2021 ◽  
pp. 1-7
Author(s):  
Shazma Khan ◽  
Sara Khan
Keyword(s):  
Developing Countries ◽  
Brain Mri ◽  
Tertiary Care ◽  
Rapid Onset ◽  
Spongiform Encephalopathy ◽  
Care Hospital ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Missed Diagnosis ◽  
Atypical Presentations

<b><i>Introduction:</i></b> Sporadic Creutzfeldt-Jakob disease (sCJD) is a transmissible disorder of the central nervous system caused by the transformation of normal prion protein into an abnormal misfolded form. The process begins spontaneously and runs a vicious cycle to cause spongiform encephalopathy, rapidly resulting in death. Amply described in the western literature, CJD is scarcely reported in Asia due to certain limitations including missed diagnosis, under-reporting, and rarity of the disease. Brain MRI, electroencephalogram, cerebrospinal fluid testing, and biopsy of the infected brain tissue support the diagnosis in cases of clinical suspicion. However, the diagnosis can still be made with limited available resources in developing countries. <b><i>Method:</i></b> A review of CJD cases evaluated in the neurology department of a tertiary care hospital in Pakistan was done from 2002 to 2018. <b><i>Results:</i></b> Eleven cases labeled as sCJD are identified based on the European MRI-CJD consortium criteria. This is the first study on CJD from Pakistan, which includes both the typical and atypical presentations. <b><i>Conclusion:</i></b> Even with limited testing available, the diagnosis of CJD can be made with confidence in the developing countries, provided the suspicion is kept high in cases of rapid onset dementia and acute behavioral changes.

scholarly journals Atypical Creutzfeldt-Jakob Disease Evolution after Electroconvulsive Therapy for Catatonic Depression

2011 ◽  
Vol 2011 ◽  
pp. 1-3 ◽  
Author(s):  
Iria Grande ◽  
Juan Fortea ◽  
Ellen Gelpi ◽  
Itziar Flamarique ◽  
Marc Udina ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Disease Duration ◽  
Psychiatric Symptoms ◽  
Psychiatric Admission ◽  
Disease Evolution ◽  
Clinical Recovery ◽  
Jakob Disease ◽  
Magnetic Resonance Imaging Mri ◽  
Electroencephalogram Eeg ◽  
Codon 129

We describe a case report of an 80-year-old woman who presented with symptomatology compatible with an episode of major depression with catatonia. After psychiatric admission, electroconvulsive therapy (ECT) was applied, but symptoms progressed with cognitive impairment, bradykinesia, widespread stiffness, postural tremor, and gait disturbance. After compatible magnetic resonance imaging (MRI), diffusion changes, and electroencephalogram (EEG) findings the case was reoriented to Creutzfeldt-Jakob disease (CJD). The genetic study found a methionine/valine heterozygosity at codon 129 of the prion protein gene PrPSc. On followup, a significant clinical recovery turned out. For this reason, EEG and MRI were repeated and confirmed the findings. The patient subsequently demonstrated progressive clinical deterioration and died 21 months later. The diagnosis was verified postmortem by neuropathology. The vCJD subtype MV2 is indeed characterized by early and prominent psychiatric symptoms and a prolonged disease duration however no frank clinical recovery has before been reported.

scholarly journals Aspergillosis of the central nervous system in a previously healthy patient that simulated Creutzfeldt-Jakob disease

2016 ◽  
Vol 7 (40) ◽  
pp. 940 ◽  
Author(s):  
SergioV Esparza-Gutiérrez ◽  
Adrián Santana-Ramírez ◽  
Pedro Avila-Rodríguez ◽  
JEugenio Jiménez-Gómez ◽  
Ezequiel Vélez-Gómez ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Healthy Patient ◽  
Jakob Disease ◽  
The Central Nervous System

Codon 129 Polymorphism Specific Cerebrospinal Fluid Proteome Pattern in Sporadic Creutzfeldt−Jakob Disease and the Implication of Glycolytic Enzymes in Prion-Induced Pathology

2010 ◽  
Vol 9 (11) ◽  
pp. 5646-5657 ◽  
Author(s):  
Joanna Gawinecka ◽  
Jana Dieks ◽  
Abdul R. Asif ◽  
Julie Carimalo ◽  
Uta Heinemann ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Glycolytic Enzymes ◽  
Jakob Disease ◽  
Codon 129

Primary Angiitis of the Central Nervous System Mimicking Sporadic Creutzfeldt-Jakob Disease

2018 ◽  
Vol 32 (3) ◽  
pp. 258-261
Author(s):  
Dian He ◽  
Gang Cai ◽  
Yan Li ◽  
Qi Liu ◽  
Kang Xiao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Angiitis ◽  
Jakob Disease ◽  
The Central Nervous System

The neuroepidemiology of human prion disease

2020 ◽  
pp. 367-378
Author(s):  
Patrick JM Urwin ◽  
Anna M Molesworth
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Prion Diseases ◽  
Prion Protein Gene ◽  
Human Prion Disease ◽  
Disease States ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Sporadic Disease

Human prion diseases comprise a number of rare and fatal neurodegenerative conditions that result from the accumulation in the central nervous system of an abnormal form of a naturally occurring protein, called the prion protein. The diseases occur in genetic, sporadic, and acquired forms: genetic disease is associated with mutations in the prion protein gene (PRNP); sporadic disease is thought to result from a spontaneous protein misfolding event; acquired disease results from transmission of infection from an animal or another human. The potential transmissibility of the prion in any of these forms, either in disease states or during the incubation period, has implications for public health. Here we focus on Creutzfeldt-Jakob Disease (CJD), including variant Creutzfeldt-Jakob Disease (vCJD), although we will also discuss other forms of human prion disease.

scholarly journals Molecular Characterization of the Danish Prion Diseases Cohort With Special Emphasis on Rare and Unique Cases

2019 ◽  
Vol 78 (11) ◽  
pp. 980-992 ◽  
Author(s):  
Aušrinė Areškevičiūtė ◽  
Helle Broholm ◽  
Linea C Melchior ◽  
Anna Bartoletti-Stella ◽  
Piero Parchi ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Prion Disease ◽  
Prion Diseases ◽  
The Past ◽  
Disease Biology ◽  
Fresh Frozen ◽  
Jakob Disease ◽  
Disease Subtypes ◽  
Codon 129

Abstract The purpose of this study was to perform an updated reclassification of all definite prion disease cases with available fresh-frozen samples referred to the Danish Reference Center over the past 40 years, putting a special emphasis on the molecular characterization of novel disease subtypes. Investigation of the Danish prion diseases cohort revealed rare sporadic Creutzfeldt-Jakob disease cases with mixed subtypes and subtypes with previously uncharacterized white matter plaques, a new case of sporadic fatal insomnia, and 3 novel mutations, including 2 large octapeptide repeat insertions, and a point mutation in the prion protein gene. The evaluation of methionine and valine distribution at codon 129 among the prion disease patients in the cohort revealed the increased prevalence of methionine homozygotes compared to the general population. This observation was in line with the prevalence reported in other Caucasian prion disease cohort studies. Reclassification of the old prion diseases cohort revealed unique cases, the molecular characterization of which improves prion diseases classification, diagnostic accuracy, genetic counseling of affected families, and the understanding of disease biology.

scholarly journals Creutzfeldt-Jakob disease: a survey of 14 patients

1996 ◽  
Vol 54 (4) ◽  
pp. 577-583 ◽  
Author(s):  
Paulo E. Marchiori ◽  
Noboru Yasuda ◽  
Helga C. A. Azevedo ◽  
Mônica Órfão ◽  
Dagoberto Callegaro ◽  
...  
Keyword(s):  
Nervous System ◽  
Gamma Globulin ◽  
Clinical Findings ◽  
Status Spongiosus ◽  
Eeg Activity ◽  
School Of Medicine ◽  
Jakob Disease ◽  
The Central Nervous System ◽  
Behaviour Changes ◽  
Visual Disturbances

Creutzfeldt-Jakob disease (CJD) is a transmissible disease of the nervous system causatively related to the presence of an abnormal prion protein, with dementia, myoclonic jerks, and periodic EEG activity. Fourteen patients (7 females and 7 males) ranging from 26 to 76 years of age (median 59 years) were evaluated between 1974 and 1995 at the Neurologic Clinic of São Paulo University School of Medicine. The average duration of the disease was 12 months (3.5 - 34 months). Early clinical findings were: behaviour changes in 7 patients, dementia in 4, visual disturbances in 4, vertigo in 2, tremor in 9, and dystonia in one. Advanced symptoms were dementia and myoclonus in all patients. Pyramidal tract dysfunction was found in 6, cerebellar ataxia in 2, seizures in 3, nystagmus and vertigo in 4, and peripheral nervous system involvement in 2. Atypical clinical forms were found in 5 patients. Periodic EEG activity was found in 10 patients. Cerebrospinal fluid evaluation showed pleocytosis in 1 patient, higher protein content in 2, and higher gamma globulin level in 2. In 10 patients anatomopathological evidence in the central nervous system confirmed the clinical diagnosis by presenting with status spongiosus. All except one patient presented with the sporadic form of the disease.

scholarly journals Sporadic Creutzfeldt-Jakob Disease: Prion Pathology in Medulla Oblongata—Possible Routes of Infection and Host Susceptibility

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Diego Iacono ◽  
Sergio Ferrari ◽  
Matteo Gelati ◽  
Gianluigi Zanusso ◽  
Sara Mariotto ◽  
...  
Keyword(s):  
Prion Protein ◽  
Environmental Exposure ◽  
Phenotypic Variability ◽  
Host Susceptibility ◽  
Motor Nucleus ◽  
Host Genotype ◽  
Dorsal Motor Nucleus ◽  
Jakob Disease ◽  
Medullary Nuclei ◽  
Codon 129

Sporadic Creutzfeldt-Jakob disease (sCJD), the most frequent human prion disorder, is characterized by remarkable phenotypic variability, which is influenced by the conformation of the pathologic prion protein and the methionine/valine polymorphic codon 129 of the prion protein gene. While the etiology of sCJD remains unknown, it has been hypothesized that environmental exposure to prions might occur through conjunctival/mucosal contact, oral ingestion, inhalation, or simultaneous involvement of the olfactory and enteric systems. We studied 21 subjects with definite sCJD to assess neuropathological involvement of the dorsal motor nucleus of the vagus and other medullary nuclei and to evaluate possible associations with codon 129 genotype and prion protein conformation. The present data show that prion protein deposition was detected in medullary nuclei of distinct sCJD subtypes, either valine homozygous or heterozygous at codon 129. These findings suggest that an “environmental exposure” might occur, supporting the hypothesis that external sources of contamination could contribute to sCJD in susceptible hosts. Furthermore, these novel data could shed the light on possible causes of sCJD through a “triple match” hypothesis that identify environmental exposure, host genotype, and direct exposure of specific anatomical regions as possible pathogenetic factors.

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