Author
|
Submitted to: Bioanalysis
Publication Type: Review Article Publication Acceptance Date: 11/11/2014 Publication Date: 1/1/2015 Citation: Nicholson, E.M. 2015. Detection of the disease-associated form of the prion protein in biological samples. Bioanalysis. 7(2):253-261. Interpretive Summary: Technical Abstract: Transmissible spongiform encephalopathies (TSEs) or prion diseases are neurodegenerative diseases that occur in a variety of mammals. In these diseases, a chromosomally encoded protein (PrP**c) undergoes a conformational change to the disease associated form (PrP**d), and PrP**d is capable inducing a change in additional molecules of PrP**c to the PrP**d conformation. PrP**d is thus the etiologic agent. Direct detection of PrP**d in biologic samples using antibody-based methods is the only currently accepted method by which a TSE may be diagnosed. Distribution of PrP**d in an affect host is not uniform and only those tissues with the highest levels of PrP**d are suitable for diagnosis. In most cases only CNS tissues harbor sufficient PrP**d for detection and CNS tissues are generally only available post-mortem. Further complicating the detection of PrP**d in biologic samples is the concurrent presence of PrP**c which cross reacts with most available antibodies. Various methods to either differentiate the PrP isoforms or eliminate PrP**c detection may be employed depending upon method chosen to detect PrP**d. Methods have been developed that either amplify the levels of PrP**d in the sample or base detection of PrP**d upon a resultant loss of function. To date, none of these approaches has resulted in a validated diagnostic test, but all have the potential to enhance sensitivity to the point where PrP**d may be readily detected antemortem and likely represent the future of TSE diagnostics. |
