NR AWFY
AU Green,A.J.E.; Ritchie,D.L.; Goodall,C.A.; Ironside,J.W.
TI Tau deposits in variant Creutzfeldt-Jakob disease - immunohistochemical and biochemical characterization
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-20
PT Konferenz-Poster
AB
The deposition of hyperphosphorylated tau around PrP plaques in variant CJD (vCJD) has been previously described (1). The aim of this study is to investigate whether these deposits are unique to vCJD or whether they can found in other forms of prion disease associated with PrP plaques. Twelve patients with vCJD (age 16-62 years, disease duration 6-20 months), 8 patients with sporadic CJD (4 MM1: age 60-75 years, disease duration 2-8 months; 4 MV2A: age 42-71 years, disease duration 7-42 months) and 2 patients with GSS (P102L mutations: age 44-45 years, disease duration 8-89 months) were investigated. Tau immunohistochemistry was performed using 10m brain sections using AT8 (phosphorylated epitopes 199-205) and pS404 (recognising phospho-tau at serine404). Immunohistochemical analysis of PrPres was undertaken using 6H4. Tau protein was extracted as from the frontal cortex and subjected to SDS-PAGE with immunoblotting with AT8 and pS404.Widespread clusters of tau deposits associated with PrP amyloid deposits were found in the frontal cortex of vCJD patients. These immuno-reactive tau species were seen in fine neuritic processes. Similar deposits were also seen in the molecular and granular layer of the cerebellum. Smaller numbers of tau deposits were also seen in the frontal cortex of MV2A sCJD patients, although these were less clustered in nature. These deposits were also seen in association with PrP plaques. In contrast, there were only a few tau reactive species found in the cerebellum of MV2A sCJD patients. The GSS cases that were examined showed sparse tau immunolabelling. None of the MM1 sCJD cases examined showed any similar tau deposits. Western blotting of the tau extracted from the frontal cortex of vCJD patients detected four pS404 reactive bands (60, 56, 54 and 50kDa). A similar pattern was seen in some of the MV2A sCJD and GSS cases. These results suggest that tau deposition is found in vCJD and may also be found in other prion diseases associated with PrP plaques. The extent of tau immunoreactivity is more widespread in vCJD and may reflect the unique morphology and the large numbers of plaques found in this condition.
(1). G.Giaccone et al. Neuroprion 2005
AD The National CJD Surveillance Unit, University of Edinburgh, Western General Hospital, Edinburgh, UK. E-mail: Alison.Green@ed.ac.uk
SP englisch
PO Italien