Amplified Detection of Prions and Other Amyloids by RT-QuIC in Diagnostics and the Evaluation of Therapeutics and Disinfectants

Caughey, Byron; Orrú, Christina D.; Groveman, Bradley R.; Hughson, Andrew G.; Manca, Matteo; Raymond, Lynne D.; Raymond, Gregory J.; Race, Brent; Saijo, Eri; Kraus, Allison

doi:10.1016/bs.pmbts.2017.06.003

Cited by 24 publications

(11 citation statements)

References 60 publications

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“…The recent introduction of in vitro assays based on the ultrasensitive, amplified measurement of pathological protein aggregates in biospecimens provided novel accurate diagnostic methods for protein‐folding diseases such as prion diseases and synucleinopathies . Among them, the prion real‐time quaking‐induced conversion (RT‐QuIC) assay is emerging as the most accurate test for the in vivo diagnosis of Creutzfeldt–Jakob disease (CJD), the most common human prion disease.…”

Section: Introductionmentioning

confidence: 99%

Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients

Mammana

Baiardi

Rossi

et al. 2020

Ann Clin Transl Neurol

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Prion real-time quaking-induced conversion (RT-QuIC) is an ultrasensitive assay detecting pathological aggregates of misfolded prion protein in biospecimens. We studied 71 punch biopsy skin samples of 35 patients with Creutzfeldt-Jakob disease (CJD), including five assessed in vitam. The results confirmed the high value of skin prion RT-QuIC for CJD diagnosis (89% sensitivity and 100% specificity) and support its use in clinical practice. Preliminary data based on a limited number of cases suggest that prion-seeding activity in the skin varies according to the prion strain, being higher in sporadic CJD subtypes linked to the V2 strain (VV2 and MV2K) than in typical CJDMM1.

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Section: Introductionmentioning

confidence: 99%

Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients

Mammana

Baiardi

Rossi

et al. 2020

Ann Clin Transl Neurol

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“…To implement this strategy, we and others have developed prototypic amplification assays for several types of protein aggregates that can serve as disease biomarkers (5)(6)(7)(8)(9)(10)(11). In these assays, a biospecimen (e.g., brain homogenate [BH], cerebrospinal fluid [CSF], or nasal brushings) containing as little as attogram amounts of the protein aggregates to be detected is added to a mixture containing a vast excess of the corresponding protein monomer (the substrate) that can build onto the seed.…”

mentioning

confidence: 99%

Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons

Metrick

Ferreira²,

Saijo³

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Recent work with prion diseases and synucleinopathies indicates that accurate diagnostic methods for protein-folding diseases can be based on the ultrasensitive, amplified measurement of pathological aggregates in biospecimens. A better understanding of the physicochemical factors that control the seeded polymerization of such aggregates, and their amplification in vitro, should allow improvements in existing assay platforms, as well as the development of new assays for other proteopathic aggregates. Here, we systematically investigated the effects of the ionic environment on the polymerization of tau, α-synuclein, and the prion protein (PrP) induced by aggregates in biospecimens. We screened salts of the Hofmeister series, a relative ordering of strongly and weakly hydrated salts that tend to precipitate or solubilize proteins. We found that sensitivities of tau-based assays for Alzheimer’s seeds and PrP-based assays for prions were best in weakly hydrated anions. In contrast, we saw an inverse trend with different tau-based assays, improving detection sensitivity for progressive supranuclear palsy seeds by ≈106. Hofmeister analysis also improved detection of sporadic Creutzfeldt–Jakob disease prions in human nasal brushings and chronic wasting disease prions in deer-ear homogenates. Our results demonstrate strong and divergent influences of ionic environments on the amplification and detection of proteopathic seeds as biomarkers for protein-folding diseases.

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“…Unfortunately, there is yet no accurate molecular or clinical in vivo biomarker for synucleinopathies. Cerebrospinal fluid measures of α‐synuclein have a large overlap with normal subjects, but there is hope for promising methods currently in development, including “seeding” assays for biofluids . A PET ligand does not appear to be imminently available .…”

mentioning

confidence: 99%

Importance of low diagnostic Accuracy for early Parkinson's disease

Beach

Adler

2018

Movement Disorders

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Amplified Detection of Prions and Other Amyloids by RT-QuIC in Diagnostics and the Evaluation of Therapeutics and Disinfectants

Cited by 24 publications

References 60 publications

Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients

Detection of prions in skin punch biopsies of Creutzfeldt–Jakob disease patients

Million-fold sensitivity enhancement in proteopathic seed amplification assays for biospecimens by Hofmeister ion comparisons

Importance of low diagnostic Accuracy for early Parkinson's disease

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