scholarly journals Prion disease resembling frontotemporal dementia and parkinsonism linked to chromosome 17

2001 ◽  
Vol 59 (2A) ◽  
pp. 161-164 ◽  
Author(s):  
Ricardo Nitrini ◽  
Luís Sidônio Teixeira da Silva ◽  
Sérgio Rosemberg ◽  
Paulo Caramelli ◽  
Paulo Eduardo Mestrinelli Carrilho ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Clinical Features ◽  
Prion Disease ◽  
Prion Diseases ◽  
Age At Onset ◽  
Abnormal Behavior ◽  
Chromosome 17 ◽  
Progressive Dementia ◽  
Behavioral Disturbances ◽  
Presenting Symptoms

OBJECTIVE: To compare the clinical features of a familial prion disease with those of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). BACKGROUND: Prion diseases are not usually considered in the differential diagnosis of FTDP-17, since familial Creutzfeldt-Jakob disease (CJD), the most common inherited prion disease, often manifests as a rapidly progressive dementia. Conversely, FTDP-17 usually has an insidious onset in the fifth decade, with abnormal behavior and parkinsonian features. METHOD: We present the clinical features of 12 patients from a family with CJD associated with a point mutation at codon 183 of the prion protein gene. RESULTS: The mean age at onset was 44.0 ± 3.7; the duration of the symptoms until death ranged from two to nine years. Behavioral disturbances were the predominant presenting symptoms. Nine patients were first seen by psychiatrists. Eight patients manifested parkinsonian signs. CONCLUSION: These clinical features bear a considerable resemblance to those described in FTDP-17.

Clinical and Genetic Aspects of Progressive Supranuclear Palsy

1998 ◽  
Vol 11 (2) ◽  
pp. 107-114 ◽  
Author(s):  
Irene Litvan ◽  
Michael Hutton
Keyword(s):  
Linkage Disequilibrium ◽  
Diagnostic Accuracy ◽  
Progressive Supranuclear Palsy ◽  
Frontotemporal Dementia ◽  
Clinical Features ◽  
Neuronal Degeneration ◽  
Chromosome 17 ◽  
Clinical Criteria ◽  
Degenerative Parkinsonism ◽  
Research Studies

Progressive supranuclear palsy (PSP) is, after Parkinson's disease, the most common form of degenerative parkinsonism. Several clinical features are used in the recognition of this disorder as well as in the differentiation from related disorders. Clinical criteria that could increase diagnostic accuracy in research studies are also emphasized. Due to a better understanding of the genetic aspects of PSP, recent studies have suggested that it is a recessive disorder in linkage disequilibrium with the tau (τ) gene, rather than a sporadic disorder. In addition, the recent identification of mutations in the τ gene associated with a similar neurodegenerative condition (frontotemporal dementia and parkinsonism linked to chromosome 17) has further strengthened the argument that τ dysfunction is somehow involved in the pathogenesis of PSP. Nongenetic factors that could trigger or perpetuate the cascade of events leading to neuronal degeneration in PSP are also reviewed.

Clinical Features and Pathogenesis of Prion Disease

2013 ◽  
pp. 915-921
Author(s):  
Joel C. Watts ◽  
Michael D. Geschwind
Keyword(s):  
Mental Illness ◽  
Neurodegenerative Diseases ◽  
Clinical Features ◽  
Prion Disease ◽  
Prion Diseases ◽  
Historical Background ◽  
Prominent Feature ◽  
Human Prion Disease

Prion diseases are uniformly fatal neurodegenerative diseases that typically are rapidly progressive. They are unique in the annals of medicine in that they occur in three ways: sporadic, genetic, and acquired. The reader might ask why prion diseases are included in a textbook on mental illness. As we will try to show in this chapter, psychiatric features are often an early and prominent feature of many prion diseases, although sometimes these features are overshadowed by the more obvious neurological, particularly cognitive and motor, features. The most common form of human prion disease is called sporadic Jakob-Creutzfeldt disease (sCJD), which comprises about 85-90% of all human prion diseases, followed by genetic forms comprising about 10-15%, and lastly acquired forms, which although the most notorious, are the least common at less than 1% 1. Before discussing these different presentations of prion disease, we will present some historical background on prion diseases, including discussing relevant nomenclature.

Prion disease

2020 ◽  
pp. 414-423
Author(s):  
Akin Nihat ◽  
TzeHow Mok ◽  
John Collinge
Keyword(s):  
Neurodegenerative Diseases ◽  
Clinical Features ◽  
Prion Disease ◽  
Prion Diseases ◽  
Clinical Criteria ◽  
Fluid Analysis ◽  
Protein Polymerization ◽  
Weighted Magnetic Resonance Imaging ◽  
Jakob Disease ◽  
Anxiety Depression

Prion diseases are fatal neurodegenerative conditions that may arise sporadically or be inherited or acquired by environmental exposure to infectious prions—transmissible agents composed of multimeric assemblies of misfolded protein. The core clinical features are progressive cognitive decline, accompanied with ataxia, myoclonus, and pyramidal or extra-pramidal motor signs. While the most common form—sporadic Creutzfeldt–Jakob disease—is generally rapidly progressive over weeks or months, inherited prion diseases can span many years, with diverse clinical features readily mimicking other neurodegenerative diseases. Psychiatric features, including agitation, anxiety, depression, hallucinations, and behavioural disturbances, are common in the early stages. Diagnosis can usually be made with confidence by the combination of clinical criteria, diffusion-weighted magnetic resonance imaging, electroencephalogram, and specialized cerebrospinal fluid analysis. Inherited prion disease can be confirmed with prion protein gene analysis, which should be considered in all early-onset dementing and ataxic conditions. It is now becoming clear that the fundamental molecular pathogenesis—seeded protein polymerization—is relevant to other neurodegenerative diseases, notably Alzheimer’s disease.

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.

Creutzfeldt-Jakob Disease in Scotland and Northern Ireland 1980–1989

1992 ◽  
Vol 37 (6) ◽  
pp. 181-184 ◽  
Author(s):  
T.G. Esmonde ◽  
R.G. Will
Keyword(s):  
Northern Ireland ◽  
Clinical Features ◽  
Age At Onset ◽  
Sex Distribution ◽  
Female Ratio ◽  
Presenting Symptoms ◽  
Close Proximity ◽  
Male Female Ratio ◽  
Jakob Disease ◽  
Duration Of Disease

The epidemiological and clinical features of Creutzfeldt-Jakob disease have never before been studied in Scotland and Northern Ireland. Case records for those dying with this diagnosis were obtained for the period 1980–89. Over the ten year period, 25 definite or probable cases were identified, giving an annual incidence of 0.37 cases/million. There were more cases in the second half of the decade, and this was most likely due to increased ascertainment. One pair of cases occurred in close proximity to each other. Sex distribution showed an excess of males (male female ratio = 1.8: 1). Mean age at onset was 65.2 years, and mean duration of disease was 5.3 months. The presenting symptoms and clinical features were similar to those noted in previous studies of other populations. There was no excess of cases in occupations linked to food, farming, or medical/paramedical work.

scholarly journals P.009 Improving Detection of Creutzfeldt-Jakob Disease Mimics in Clinical Practice

2021 ◽  
Vol 48 (s3) ◽  
pp. S22-S22
Author(s):  
ES Lazar ◽  
AL Porter ◽  
CC Prusinski ◽  
S Dunham ◽  
A Lopez-Chiriboga ◽  
...  
Keyword(s):  
Clinical Features ◽  
Autoimmune Encephalitis ◽  
Motor Dysfunction ◽  
Mri Findings ◽  
Progressive Dementia ◽  
Clinical Criteria ◽  
Presenting Symptoms ◽  
Jakob Disease ◽  
Study Sites ◽  
Motor Abnormalities

Background: Assays capable of detecting prions in CSF (e.g., RT-QuIC) have greatly improved the antemortem diagnosis of Creutzfeldt-Jakob disease (CJD) yet take time to conduct and are not widely accessible. There is a need to identify clinical features and common tests that identify mimics at presentation. Methods: Mimics were identified within longitudinal studies of rapidly progressive dementia at study sites. Mimics met clinical criteria for probable CJD but did not have CJD. Clinical features were compared between mimics and patients with CJD assessed at Mayo Clinic Enterprise (n=79) and Washington University in St. Louis (n=10; Jan-2014 to Oct-2020). Results: Mimics (10/155; 6.5%) were diagnosed with autoimmune encephalitis (n=7), neurosarcoidosis, frontotemporal lobar degeneration with motor neuron disease, and unknown dementia. Age-at-symptom onset, gender, presenting symptoms, and EEG and MRI findings were similar between mimics and CJD patients. Focal motor abnormalities (49/93, 10/10), elevations in CSF leukocytosis (4/92, 5/10) and protein (39/92, 9/10) were more common in mimics (p<0.01). Neural-specific autoantibodies associated with autoimmune encephalitis were detected within the serum (4/9) and CSF (5/10) of mimics, but not CJD cases. Conclusions: Autoimmune encephalitis, neurosarcoidosis and neurodegenerative diseases may mimic CJD at presentation and should be considered in patients with early motor dysfunction and abnormal CSF studies.

scholarly journals Therapeutic Assay with the Non-toxic C-Terminal Fragment of Tetanus Toxin (TTC) in Transgenic Murine Models of Prion Disease

2021 ◽  
Author(s):  
Marina Betancor ◽  
Laura Moreno-Martínez ◽  
Óscar López-Pérez ◽  
Alicia Otero ◽  
Adelaida Hernaiz ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurodegenerative Diseases ◽  
Prion Disease ◽  
Tetanus Toxin ◽  
Neuronal Survival ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Murine Models ◽  
Terminal Fragment ◽  
Lateral Sclerosis

AbstractThe non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrPC) into an abnormal and misfolded isoform known as PrPSc. These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrPC, were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models.

scholarly journals Detection of Prions in Brain Homogenates and CSF Samples Using a Second-Generation RT-QuIC Assay: A Useful Tool for Retrospective Analysis of Archived Samples

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 750
Author(s):  
Tibor Moško ◽  
Soňa Galušková ◽  
Radoslav Matěj ◽  
Magdalena Brůžová ◽  
Karel Holada
Keyword(s):  
Retrospective Analysis ◽  
Prion Disease ◽  
Second Generation ◽  
Prion Diseases ◽  
Neuropsychiatric Symptoms ◽  
Final Diagnosis ◽  
Post Mortem ◽  
Long Term Storage ◽  
Archived Samples

The possibilities for diagnosing prion diseases have shifted significantly over the last 10 years. The RT-QuIC assay option has been added for neuropsychiatric symptoms, supporting biomarkers and final post-mortem confirmation. Samples of brain homogenates used for final diagnosis, archived for many years, provide the possibility for retrospective studies. We used a second-generation RT-QuIC assay to detect seeding activity in different types of sporadic and genetic prion diseases in archival brain homogenates and post-mortem CSF samples that were 2 to 15 years old. Together, we tested 92 archival brain homogenates: 39 with definite prion disease, 28 with definite other neurological disease, and 25 with no signs of neurological disorders. The sensitivity and specificity of the assay were 97.4% and 100%, respectively. Differences were observed in gCJD E200K, compared to the sporadic CJD group. In 52 post-mortem CSF samples—24 with definite prion disease and 28 controls—we detected the inhibition of seeding reaction due to high protein content. Diluting the samples eliminated such inhibition and led to 95.8% sensitivity and 100% specificity of the assay. In conclusion, we proved the reliability of archived brain homogenates and post-mortem CSF samples for retrospective analysis by RT-QuIC after long-term storage, without changed reactivity.

scholarly journals Deletion of Kif5c Does Not Alter Prion Disease Tempo or Spread in Mouse Brain

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1391
Author(s):  
Brent Race ◽  
Katie Williams ◽  
Chase Baune ◽  
James F. Striebel ◽  
Clayton W. Winkler ◽  
...  
Keyword(s):  
Prion Disease ◽  
Molecular Motors ◽  
Prion Diseases ◽  
Mouse Strains ◽  
Survival Times ◽  
Knock Out ◽  
Transport Vesicles ◽  
The Central Nervous System ◽  
Knock Out Mice ◽  
Scrapie Strains

In prion diseases, the spread of infectious prions (PrPSc) is thought to occur within nerves and across synapses of the central nervous system (CNS). However, the mechanisms by which PrPSc moves within axons and across nerve synapses remain undetermined. Molecular motors, including kinesins and dyneins, transport many types of intracellular cargo. Kinesin-1C (KIF5C) has been shown to transport vesicles carrying the normal prion protein (PrPC) within axons, but whether KIF5C is involved in PrPSc axonal transport is unknown. The current study tested whether stereotactic inoculation in the striatum of KIF5C knock-out mice (Kif5c−/−) with 0.5 µL volumes of mouse-adapted scrapie strains 22 L or ME7 would result in an altered rate of prion spreading and/or disease timing. Groups of mice injected with each strain were euthanized at either pre-clinical time points or following the development of prion disease. Immunohistochemistry for PrP was performed on brain sections and PrPSc distribution and tempo of spread were compared between mouse strains. In these experiments, no differences in PrPSc spread, distribution or survival times were observed between C57BL/6 and Kif5c−/− mice.

Sign in / Sign up

Export Citation Format

Share Document