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Prions
Published in Dongyou Liu, Laboratory Models for Foodborne Infections, 2017
Akikazu Sakudo, Takashi Onodera
Recently, the real-time quaking-induced conversion (RT-QuIC) test [22], which is a modified version of PMCA, has been developed. This method is based on the prion-seeded fibrillization of recombinant PrP. In RT-QuIC reactions, prion-associated seeds induce the amyloid fibril formation of bacterially expressed recombinant PrP in multiwell plates. The resulting amyloid fibrils are then detected by the enhanced fluorescence of an amyloid sensitive dye, thioflavin T, present in the reaction mix. RT-QuIC is known to be highly specific and sensitive for the detection of multiple human and animal prion diseases [23]. Epidemiological surveillance of CJD, which currently relies heavily on autopsy-based diagnosis, could be more efficient, cost-effective, and broadly applicable with RT-QuIC testing for cerebrospinal fluid (CSF) samples that can be obtained without autopsies [24]. The second-generation RT-QuIC assay markedly improves the speed and sensitivity of detecting prion seeds in CSF specimens from CJD patients [24].
Prions
Published in Dongyou Liu, Handbook of Foodborne Diseases, 2018
Recently, PMCA has been refined, resulting in the development of a novel assay known as real-time quaking-induced conversion (RT-QuIC), which is a highly sensitive PrPSc detection method (i.e., 1 fg levels) [110,111]. In this method, a small amount (about 2–15 μL) of test sample is added to a reaction mixture containing recombinant PrP substrate and a detergent or chaotropic agent as well as the amyloid sensitive dye thioflavin T (ThT), whose fluorescent signal can be used to quantify amyloid formation. ThT fluorescence is monitored in real time using a fluorescence microplate reader under temperature-controlled conditions with several cycles of vigorous quaking. Because the reaction can be performed in a microtiter plate with small sample volumes, large numbers of samples can be applied to this assay. In addition, the concentration of prions can be estimated from the index of ThT fluorescence. Therefore, RT-QuIC is the preferred method for surveillance of prion diseases. Several surveillance centers have been set up using this diagnostic test for sCJD [112,113]. In addition, this assay achieved >95% sensitivity and 100% specificity using cerebrospinal fluid [114,115] and nasal brushing of CJD [116]. Recently, improvements to the RT-QuIC methodology have been made in terms of the substrate. By using recombinant bank vole PrP as universal substrate, 28 human and animal prion strains were detected at a 10−4 seed brain homogenate dilution [117]. Moreover, the assay using bank vole or hamster-related PrP could also discriminate classic and atypical BSE, scrapie, sCJD, and vCJD [117]. Thus, this method has the potential to enable preclinical and antemortem diagnosis of human and animal prion diseases using a universal procedure.
Proceedings of the 44th Annual Upper Midwest Neuro-Ophthalmology Group Meeting
Published in Neuro-Ophthalmology, 2023
Negar Moheb, Adam Baim, Collin McClelland, John. J. Chen
Khawla Abusamra, MBBS, University of Kentucky, presented a case of a 75-year-old woman, who was evaluated for progressive bilateral vision loss, intermittent binocular horizontal diplopia, and encephalopathy. Her visual symptoms continued despite bilateral cataract surgery. She underwent an unrevealing full stroke work up. Over the next 8 weeks she developed prosopagnosia, visual agnosia, unsteady gait, numbness, generalised weakness, dysphagia, visual hallucinations, abnormal body postures, myoclonic jerks and she eventually became mute. Serological and CSF studies were notable for an elevated CSF protein, but otherwise she had a negative infectious and autoimmune work up. Repeat brain MRI revealed diffuse T2 hyperintensities and restricted diffusion with cortical ribboning throughout the cerebral cortex and parts of the deep grey nuclei, which were evident on the initial MRI in retrospect. She was diagnosed with Creutzfeldt-Jakob disease (CJD) and passed away within 2 weeks of diagnosis. Real-time quaking-induced conversion testing was indeterminate and was felt to be the result of a traumatic lumbar puncture. This case showed the typical clinical features and MRI findings of the Heidenhain variant of CJD with visual cortical and parietal predominant cortical ribboning pattern. CJD should be in the differential diagnosis for patients with rapidly progressive vision loss, cognitive decline, and other cortical signs.
Diagnostic challenge of non‐specific visual symptoms: consideration of Heidenhain variant of Creutzfeldt‐Jakob disease
Published in Clinical and Experimental Optometry, 2018
Dimitrios Ntantos, Petros Aggelopoulos, Dimitrios Kazis, Ioannis E Dagklis, Sevasti Bostantjopoulou
Recently, although not included yet in the diagnostic criteria, novel sensitive techniques have been developed offering a rapid and precise diagnosis of sCJD. Among them, the most promising one seems to be the real‐time quaking‐induced conversion which is based on the amplified detection of the PrPSc in easily accessible specimens such as CSF or olfactory epithelium.2016 New tests are also available for the variant CJD. In a recent study a prototype blood assay, based on the immunodetection of abnormal PrP captured on metal particles, has shown high specificity.2014
Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry
Published in The World Journal of Biological Psychiatry, 2018
Piotr Lewczuk, Peter Riederer, Sid E. O’Bryant, Marcel M. Verbeek, Bruno Dubois, Pieter Jelle Visser, Kurt A. Jellinger, Sebastiaan Engelborghs, Alfredo Ramirez, Lucilla Parnetti, Clifford R. Jack, Charlotte E. Teunissen, Harald Hampel, Alberto Lleó, Frank Jessen, Lidia Glodzik, Mony J. de Leon, Anne M. Fagan, José Luis Molinuevo, Willemijn J. Jansen, Bengt Winblad, Leslie M. Shaw, Ulf Andreasson, Markus Otto, Brit Mollenhauer, Jens Wiltfang, Martin R. Turner, Inga Zerr, Ron Handels, Alexander G. Thompson, Gunilla Johansson, Natalia Ermann, John Q. Trojanowski, Ilker Karaca, Holger Wagner, Patrick Oeckl, Linda van Waalwijk van Doorn, Maria Bjerke, Dimitrios Kapogiannis, H. Bea Kuiperij, Lucia Farotti, Yi Li, Brian A. Gordon, Stéphane Epelbaum, Stephanie J. B. Vos, Catharina J. M. Klijn, William E. Van Nostrand, Carolina Minguillon, Matthias Schmitz, Carla Gallo, Andrea Lopez Mato, Florence Thibaut, Simone Lista, Daniel Alcolea, Henrik Zetterberg, Kaj Blennow, Johannes Kornhuber
The test systems have been adapted to the human CSF. The real-time quaking-induced conversion (RT-QuIC) allows amplifying the minimal amount of misfolded PrP to detectable levels in a reasonable time frame of up to 80 h (Schmitz, Cramm, et al. 2016).