A novel method for preclinical detection of PrPSc in blood

Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study

“…1,[44][45][46] Because newly acquired anti-GFAP antibody response usually takes about 5 days to manifest, 26,47,48 it is unlikely that the acute post-TBI autoantibody levels we report here were from a de novo response to current TBI, but rather to a sustained increase because of previous head injuries. At present, however, we cannot rule out whether the acute TBI event might serve to be an antigen-boosting event for those with pre-existing anti-GFAP antibody titers.…”

First Demonstration of Transmissible Spongiform Encephalopathy-associated Prion Protein (PrPTSE) in Extracellular Vesicles from Plasma of Mice Infected with Mouse-adapted Variant Creutzfeldt-Jakob Disease by in Vitro Amplification

“…can reliably identify preclinical cases to minimize the risk of iatrogenic disease transmission via blood-derived products. Experimental detection of PrP TSE in animal cerebrospinal fluid (CSF) (29), whole blood (21,22), plasma (27)(28)(29)(30)71), buffy coat (24 -26), and urine (74) and in human CSF (12,75), whole blood (6 -8), and urine (76,77) has been achieved by different methods that rely on the concentration or amplification techniques to bring PrP TSE levels to the detection threshold of biochemical assays. Although the presence of PrP TSE in blood exosomes has been suggested previously (48), biochemical detection has been complicated by the low levels of PrP TSE in blood and the concomitantly large volumes required for exosome isolation by standard methods.…”

“…Under these conditions, inhibitors are diluted after each round, at the same time that new PrP TSE is generated. This approach enabled PrP TSE detection as follows: in buffy coat samples from 263K-infected hamsters during the preclinical and clinical phases of prion disease (24,25); in plasma preparations from preclinical and clinically sick scrapie-affected sheep, CWD-infected white-tailed deer (28), and from clinically ill mice infected with mouse-adapted BSE (71); in blood leukocytes from clinically sick VRQ/VRQ scrapie-affected sheep (26); and in whole blood from clinical mice infected with scrapie (21). To evaluate the effect of plasma on the detection of EV-associated PrP TSE by saPMCA, EVs isolated from conditioned media of infected cells as described above were added to 250 l of human plasma obtained from a healthy donor.…”

“…PrP TSE has been successfully detected in the following: in whole blood of experimentally infected mice and hamsters, in sheep with natural scrapie and experimental BSE, and in white-tailed deer afflicted with CWD (21)(22)(23); in buffy coats of hamsters and sheep experimentally infected with scrapie (24 -26), as well as in plasma of mice and hamsters with scrapie; and in sheep and white-tailed deer naturally and experimentally infected with scrapie and CWD, respectively (27)(28)(29)(30). However, it is still not fully understood in what blood component TSE infectivity and/or PrP TSE reside and whether and how blood contributes to the spread of the disease from the periphery to the brain.…”

Factors intrinsic and extrinsic to blood hamper the development of a routine blood test for human prion diseases

“…An interesting approach that has been recently described involves a combination of PMCA and a SOFIA (Rubenstein et al, 2010). Using this approach, the number of cycles necessary for the amplification of PrP TSE could be limited without obtaining PMCArelated false-positives after a particular number of amplification cycles; in these cases, PrP TSE also spontaneously formed in the control samples.…”