NR ATJV
AU Veith,N.; Alten,J.; Kues,A.; Kaup,F.J.; Zerr,I.; Bodemer,W.
TI Alpha-Hemoglobin-Stabilizing-Protein (AHSP) as Surrogate Marker for the Preclinical Diagnosis of Sporadic CJD in Blood
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Diagnosis DIA-07
PT Konferenz-Poster
AB Creutzfeldt-Jakob disease (CJD) as transmissible spongiform encephalopathy is a rare disease. However, it is rapidly progressing in later stages and leads to fatal neurodegeneration. Diagnosis of CJD relies on clinical examination, imaging of brain, biochemical markers in liquor and eventually on neuropathology. The latter focuses on the detection of the PrPres. Although a number of surrogate markers like S-100 or neuronal enolase are known only 14-3-3 has become a widely used marker in liquor for preclinical examination. Unexpectedly, Miele et al. (2001) have detected a differentially expressed gene, i.e. its transcript being reduced at terminal stages in scrapie-infected mice, sheep and BSE. The mRNA of the Alpha-Hemoglobin-Stabilizing-Protein (AHSP) has been determined in Northern Blot analyses with total RNA isolated from blood of TSE infected animals and their respective controls. Previously AHSP was designated EDRF and ERAF. Determination of the abundance of the AHSP mRNA, therefore, provided a putative marker that can easily be assessed in blood. Early diagnosis would then be possible. Having access to a number of CJD cases and controls we have developed a real-time RT PCR to determine the AHSP mRNA pool sizes in blood cells. We could screen about 70 sporadic CJD cases and several controls to get insight into the variation of AHSP mRNA pool size. We have seen cases with reduced AHSP mRNA abundances as expected from experimental TSE. However, we have also detected cases with a higher abundance compared to the controls. The reason for this unexpected finding is not known yet. Perhaps it is related to the genotypes of CJD, age, gender or the progression of disease (slow or fast). These parameters have not been studied so far. In contrast to a publication by Glock et al. (2003) we have standardized our real time RT PCR with hemoglobin as an appropriate reference gene and have included sporadic CJD cases.
AD N.Veith, Konstanz University (Molecular Toxicology), Germany; J.Alten, I.Zerr, University Hospital Göttingen (CJD Research Group), Germany; A.Kues, F.-J.Kaup, W.Bodemer, German Primate Center Göttingen (Infectious Pathology), Germany
SP englisch
PO Deutschland