Faculty Opinions recommendation of Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples.

2017 ◽  
Author(s):  
Robert Will ◽  
Graeme Mackenzie
Keyword(s):  
Cerebrospinal Fluid ◽  
Real Time ◽  
Prion Disease ◽  
Olfactory Mucosa ◽  
Human Prion Disease

Diagnosis of Human Prion Disease Using Real-Time Quaking-Induced Conversion Testing of Olfactory Mucosa and Cerebrospinal Fluid Samples

2017 ◽  
Vol 74 (2) ◽  
pp. 155 ◽  
Author(s):  
Matilde Bongianni ◽  
Christina Orrù ◽  
Bradley R. Groveman ◽  
Luca Sacchetto ◽  
Michele Fiorini ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Real Time ◽  
Prion Disease ◽  
Olfactory Mucosa ◽  
Human Prion Disease

scholarly journals Skin RT-QuIC Assays are More Sensitive than CSF RT-QuIC in Prion Detection for Chinese Probable Sporadic Creutzfeldt-Jakob Disease

2020 ◽  
Author(s):  
Kang Xiao ◽  
Xue-Hua Yang ◽  
Wei Zhou ◽  
Cao Chen ◽  
Brian S Appleby ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Prion Disease ◽  
Preliminary Data ◽  
High Sensitivity ◽  
Definite Diagnosis ◽  
Human Prion Disease ◽  
Diagnostic Potential ◽  
Jakob Disease ◽  
The Brain ◽  
Skin Specimen

Abstract BackgroundThe definite diagnosis of human sporadic Creutzfeldt-Jakob disease (sCJD) largely depends on postmortem neuropathology and PrPSc detection in the brain. The development of prion RT-QuIC of cerebrospinal fluid (CSF) samples makes it possible for premortem diagnosis for sCJD. However the diagnostic potential of RT-QuIC of skin specimen for probable sCJD is not well researched. This study is to evaluate the diagnostic potential of RT-QuIC of skin specimen in human prion diseases.MethodsWe collected the paired skin and CSF samples from 29 recruited alive patients referred to Chinese CJD surveillance center, including 12 probable sCJD, 9 non-CJD, 3 genetic prion disease (gPrD) and 5 cases whose diagnoses still pending. The samples were subjected to RT-QuIC assays using recombinant hamster PrP protein rHaPrP90-231 as the substrate.ResultsAll 12 probable sCJD patients, 4 pending, and 1 T188K genetic CJD (gCJD) cases showed positive prion-seeding activity, while all 9 non-CJD patients were negative. CSF RT-QuIC positive seeding activity was only observed in 5 probable sCJD patients.ConclusionsOur preliminary data indicate high sensitivity and specificity of skin RT-QuIC in prion detection for Chinese probable sCJD and highlight that skin prion-seeding activity is a reliable biomarker for premortem diagnosis of human prion disease.

The real-time quaking-induced conversion assay for detection of human prion disease and study of other protein misfolding diseases

2016 ◽  
Vol 11 (11) ◽  
pp. 2233-2242 ◽  
Author(s):  
Matthias Schmitz ◽  
Maria Cramm ◽  
Franc Llorens ◽  
Dominik Müller-Cramm ◽  
Steven Collins ◽  
...  
Keyword(s):  
Real Time ◽  
Prion Disease ◽  
Protein Misfolding ◽  
Human Prion Disease ◽  
The Real ◽  
Misfolding Diseases

scholarly journals Validation and Application of Skin RT-QuIC to Patients in China with Probable CJD

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1642
Author(s):  
Kang Xiao ◽  
Xuehua Yang ◽  
Wei Zhou ◽  
Cao Chen ◽  
Qi Shi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Prion Disease ◽  
High Sensitivity ◽  
Definite Diagnosis ◽  
Human Prion Disease ◽  
Positive Skin ◽  
Diagnostic Potential ◽  
Jakob Disease ◽  
The Brain ◽  
Skin Samples

The definite diagnosis of human sporadic Creutzfeldt–Jakob disease (sCJD) largely depends on postmortem neuropathology and PrPSc detection in the brain. The development of real-time quaking-induced conversion (RT-QuIC) of cerebrospinal fluid (CSF) samples makes it possible for premortem diagnosis for sCJD. To test the diagnostic potential of RT-QuIC of skin specimens for probable sCJD, we collected the paired skin and CSF samples from 51 recruited living patients referred to the Chinese CJD surveillance center, including 34 probable sCJD, 14 non-CJD, and 3 genetic prion disease (gPrD). The samples were subjected to RT-QuIC assays using recombinant hamster PrP protein rHaPrP90-231 as the substrate. Using skin RT-QuIC assay, 91.2% (31/34) probable sCJD patients, and 1 T188K genetic CJD (gCJD) cases showed positive prion-seeding activity, while 85.7% (12/14) non-CJD patients were negative. CSF RT-QuIC positive seeding activity was only observed in 14 probable sCJD patients. Analysis of the reactivity of 38 positive skin RT-QuIC tests revealed that the positive rates in the preparations of 10−2, 10−3 and 10−4 diluted skin samples were 88.6% (39/44), 63.6% (28/44), and 25.0% (11/44), respectively. Eleven probable sCJD patients donated two skin specimens collected at different sites simultaneously. Although 95.5% (21/22) skin RT-QuIC elicited positive reaction, the reactivity varied. Our preliminary data indicate high sensitivity and specificity of skin RT-QuIC in prion detection for Chinese probable sCJD and highlight that skin prion-seeding activity is a reliable biomarker for premortem diagnosis of human prion disease.

Diagnosis of neuroschistosomiasis by antibody specificity index and semi-quantitative real-time PCR from cerebrospinal fluid and serum

2014 ◽  
Vol 63 (2) ◽  
pp. 309-312 ◽  
Author(s):  
Georg Härter ◽  
Hagen Frickmann ◽  
Sebastian Zenk ◽  
Dominic Wichmann ◽  
Bettina Ammann ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Real Time ◽  
Real Time Pcr ◽  
Clinical Symptoms ◽  
Diagnostic Procedures ◽  
Lower Limbs ◽  
Antibody Specificity ◽  
Quantitative Real Time Pcr ◽  
Specific Antibodies ◽  
Routine Diagnosis

We describe the case of a 16-year-old German male expatriate from Ghana who presented with obstipation, dysuria, dysaesthesia of the gluteal region and the lower limbs, bilateral plantar hypaesthesia and paraesthesia without pareses. A serum–cerebrospinal fluid (CSF) Schistosoma spp. specific antibody specificity index of 3.1 was considered highly suggestive of intrathecal synthesis of anti-Schistosoma spp. specific antibodies, although standardization of this procedure has not previously been described. Diagnosis was confirmed by detection of Schistosoma DNA in CSF by semi-quantitative real-time PCR at 100-fold concentration compared with serum. Accordingly the two diagnostic procedures, which have not previously been applied for routine diagnosis, appear to be useful for the diagnosis of neuroschistosomiasis. Clinical symptoms resolved following anthelmintic and anti-inflammatory therapy.

Loss of glycosylation associated with the T183A mutation in human prion disease

2004 ◽  
Vol 108 (6) ◽  
pp. 476-484 ◽  
Author(s):  
E. Grasbon-Frodl ◽  
Holger Lorenz ◽  
U. Mann ◽  
R. M. Nitsch ◽  
Otto Windl ◽  
...  
Keyword(s):  
Prion Disease ◽  
Human Prion Disease

Molecular, Genetic and Transgenetic Studies of Human Prion Disease

1998 ◽  
pp. 303-304
Author(s):  
J. Collinge ◽  
J. Beck ◽  
T. A. Campbell ◽  
M. Desbuslais ◽  
I. Gowland ◽  
...  
Keyword(s):  
Prion Disease ◽  
Molecular Genetic ◽  
Human Prion Disease

scholarly journals Genetic human prion disease modelled in PrP transgenic Drosophila

2017 ◽  
Vol 474 (19) ◽  
pp. 3253-3267 ◽  
Author(s):  
Alana M. Thackray ◽  
Alzbeta Cardova ◽  
Hanna Wolf ◽  
Lydia Pradl ◽  
Ina Vorberg ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Disease ◽  
Prion Diseases ◽  
Principal Component ◽  
Site Directed Mutagenesis ◽  
Host Protein ◽  
Therapeutic Interventions ◽  
Proteinase K ◽  
Human Prion Disease ◽  
Transgenic Drosophila

Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt–Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrPSc, an abnormal isomer of the normal host protein PrPC, in the brain of affected individuals. PrPSc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila. We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila. Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host.

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