NR AWQZ
AU Yutzy,B.; Holznagel,E.; Coulibaly,C.; Deslys,J.P.; Hunsmann,G.; Löwer,J.
TI Detection of 14-3-3 proteins in cerebrospinal fluid is a late disease marker in experimental simian variantCJD
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions DIA-62
PT Konferenz-Poster
AB Here, we present data from a study in BSE-infected Cynomolgus monkeys. Cerebrospinal fluid (CSF) samples were collected from infected animals and tested for the presence of 14-3-3 protein isoforms as a biomarker for brain damage to identify the onset of brain damage. An in-house western immunoblot protocol was established and evaluated using 10 microl of CSF to detect 14-3-3 protein isoforms: the lower detection limit is around 0.1 ng protein/10microl CSF. CSF samples were collected from Cynomolgus monkeys at regular intervals during the asymptomatic and symptomatic phase of infection. False-positive results were obtained by cell-contaminated CSF samples, whereas falsenegative results were seen in samples after repeated freeze-thaw cycles. For the study, freshly obtained CSF samples were carefully tested for cell contaminations, aliquoted and one aliquot was tested on the day of collection. The incubation period (1000 - 1800 days) was defined as the period from the BSE inoculation until the drop in body weight, since the onset of the symptomatic phase of infection was characterized by this drop in body weight rather than by CNS symptoms. The decline in the body weight was followed by behavioural changes and finally by ataxia one to four months later. Monkeys with ataxia were sacrificed and simian vCJD was confirmed at necropsy by the detection of both typical lesion profiles and PrPres in the brain. 14-3-3 protein-positive CSF samples were found exclusively during the phase of behavioural changes and ataxia but not earlier. In conclusion, 14-3-3 proteins are detectable in small amounts of simian CSF samples. However, pathological changes occur earlier than detectable brain damage. Finally, the detection of 14-3-3 proteins in CSF samples is a tool suitable for defining and standardizing the humane endpoint in experimental simian vCJD. The work referenced was performed in partial fulfilment of the study "BSE in primates" supported by the EU (QLK1-2002-01096).
AD B. Yutzy, E. Holznagel, C. Coulibaly, J. Löwer: Paul-Ehrlich-Institut, Langen, Germany; J.-P. Deslys: Commissariat à l'Energie Atomique, Fontenay-aux-Roses, France; G. Hunsmann: German Primate Centre (DPZ), Göttingen, Germany. E-mail: yutba@pei.de
SP englisch
PO Italien