Apolipoprotein E and other cerebrospinal fluid proteins differentiate ante mortem variant Creutzfeldt-Jakob disease from ante mortem sporadic Creutzfeldt-Jakob disease

Abstract

The ability to perform an ante mortem differential diagnosis of Creutzfeld-Jakob disease (CJD) is aided by several clinical and molecular tests. There is a need for molecular tests which can reliably distinguish ante mortem variant CJD (vCJD) from ante mortem sporadic CJD (spCJD). A proteomics approach employing two-dimensional protein electrophoresis is applied to the study of ante mortem CSF samples obtained in collaboration with the CJD Surveillance Unit and the National Hospital for Neurology and Neurosurgery. The sample set includes two cases of vCJD, three cases of spCJD and three neurologic controls. Preliminary data using a panel of seven molecular markers is able to distinguish vCJD from spCJD using a heuristic clustering algorithm. One of the molecular markers has been identified as apolipoprotein E which appears to be upregulated in the cerebrospiral fluid (CSF) of patients with vCJD as compared to spCJD. Analysis of ante mortem CSF may help to differentiate patients with vCJD from those patients with spCJD.

The use of non-prion biomarkers for the diagnosis of Transmissible Spongiform Encephalopathies in the live animal

“…However, similar findings were reported by Hochstrasser et al [44]. Choe et al [23] recently demonstrated increased concentrations of ApoE in the CSF of vCJD patients but not patients with sCJD.…”

Human body fluid proteome analysis

“…A follow-up study by 2-DE/Western blotting revealed multiple isoforms of 14-3-3 protein (14-3-3 beta, gamma, epsilon, and eta) were all present in the CSF of patients with CJD, and specific 14-3-3 isoform patterns could be used to differentiate CJD from other neurodegenerative diseases [350]. A panel of seven CSF proteins, including apo E, were found capable of distinguishing ante mortem variant CJD from ante mortem sporadic CJD [351]. The cellular prion protein (PrPc) is a glycosylphosphatidylinositol-anchored glycoprotein, which represents the substrate for the generation of a conformational pathogenic isoform (PrPsc) in prion diseases.…”

Proteomics analysis of human cerebrospinal fluid

“…(2) Dialysis: overnight dialysis was performed with a membrane (cut-off mass: 3.5 kDa), and proteins were either precipitated with acetone [7] or were concentrated with a vacuum [8]. (3) Protein precipitation: a CSF sample was incubated with icecold acetone [6,9], TCA in acetone [9], or ethanol [10]. After centrifugation, proteins were precipitated.…”