The difficulty in developing a diagnostic assay for
Creutzfeldt - Jakob disease (CJD) and other
transmissible spongiform encephalopathies (TSEs) stems in part from the fact that the infectious agent is an aberrantly folded form of an endogenous cellular
protein. This precludes the use of the powerful gene based technologies currently applied to the direct detection of other infectious agents. To circumvent this problem our research objective has been to identify a set of
proteins exhibiting characteristic differential abundance in response to TSE
infection. The objective of the present study was to assess the disease specificity of differentially abundant urine
proteins able to identify
scrapie infected mice. Two-dimensional differential gel electrophoresis was used to analyze longitudinal collections of urine samples from both
prion-infected mice and a transgenic mouse model of
Alzheimer's disease. The introduction of
fluorescent dyes, that allow multiple samples to be co-resolved and visualized on one two dimensional gel, have increased the accuracy of this methodology for the discovery of robust
protein biomarkers for disease. The accuracy of a small panel of differentially abundant
proteins to correctly classify an independent naïve sample set was determined. The results demonstrated that at the time of clinical presentation the differential abundance of urine
proteins were capable of identifying the
prion infected mice with 87% sensitivity and 93% specificity. The identity of the diagnostic differentially abundant
proteins was investigated by mass spectrometry.