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Atypical prion protein conformation in familial prion disease with PRNP P105T mutation


Polymenidou, M; Prokop, S; Jung, H H; Hewer, E; Peretz, D; Moos, R; Tolnay, M; Aguzzi, A (2011). Atypical prion protein conformation in familial prion disease with PRNP P105T mutation. Brain Pathology, 21(2):209-214.

Abstract

Protease-resistant prion protein (PrP(Sc) ) is diagnostic of prion disease, yet its detection is frequently difficult. Here, we describe a patient with a PRNP P105T mutation and typical familial prion disease. Brain PrP(Sc) was undetectable by conventional Western blotting and barely detectable after phosphotungstate precipitation, where it displayed an atypical pattern suggestive of noncanonical conformation. Therefore, we used a novel misfolded protein assay (MPA) that detects PrP aggregates independently of their protease resistance. The MPA revealed the presence of aggregated PrP in similar amounts as in typical sporadic Creutzfeldt-Jakob disease. These findings suggest that measurements of PrP aggregation with the MPA may be potentially more sensitive than protease-based methodologies.

Protease-resistant prion protein (PrP(Sc) ) is diagnostic of prion disease, yet its detection is frequently difficult. Here, we describe a patient with a PRNP P105T mutation and typical familial prion disease. Brain PrP(Sc) was undetectable by conventional Western blotting and barely detectable after phosphotungstate precipitation, where it displayed an atypical pattern suggestive of noncanonical conformation. Therefore, we used a novel misfolded protein assay (MPA) that detects PrP aggregates independently of their protease resistance. The MPA revealed the presence of aggregated PrP in similar amounts as in typical sporadic Creutzfeldt-Jakob disease. These findings suggest that measurements of PrP aggregation with the MPA may be potentially more sensitive than protease-based methodologies.

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9 citations in Web of Science®
14 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2011
Deposited On:20 Jan 2011 08:32
Last Modified:05 Apr 2016 14:28
Publisher:Wiley-Blackwell
ISSN:1015-6305
Publisher DOI:https://doi.org/10.1111/j.1750-3639.2010.00439.x
PubMed ID:20875062
Permanent URL: https://doi.org/10.5167/uzh-39979

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