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In vitro conversion assays diagnostic for neurodegenerative proteinopathies

A review of RT-QuIC and PMCA assays for Alzheimer's disease, Parkinson's disease, Pick's disease, and Creutzfeldt-Jakob disease.



Check out our recent publication reviewing in vitro conversion assays, including real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA) techniques. These assays exploit the intrinsic property of prion proteins to propagate their misfolded structure.


Singh S & DeMarco ML. In vitro conversion assays diagnostic for neurodegenerative proteinopathies. Journal of Applied Laboratory Medicine. 2020;5(1):142-157.


CONCLUSIONS

This review highlights in vitro conversion diagnostic assays for alpha-synuclein-, amyloid-beta-, and tau-opathies and those advancements in the prion field that will help guide future research. RT-QuIC and PMCA boast several practical advantages over other diagnostic techniques like imaging or quantification of monomeric protein biomarkers in CSF, such as (a) easy to interpret binary results, (b) small sample volumes required, (c) analytical sensitivity to detect in the prodromal stage of disease, and (d) use of automation and simple instrumentation. Complicating factors for clinical implementation include (i) finicky and costly assay reagents, often requiring in-house synthesis/expression and purification, (ii) assay run times of hours to days, and (iii) challenges in characterizing potential assay interferents (i.e., inhibitors/accelerators of aggregation).



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