NR ARYF
AU Yang,S.L.; Mastrianni,J.A.; DeArmond,S.J.
TI Neuropathological changes colocalize with deposition of PrPcJD and loss of PrPc in Creutzfeldt-Jakob-disease
QU Journal of Neuropathology and Experimental Neurology 1996; 55(N5): 636 Nr. 123
PT Meeting Abstract
VT
NEUROPATHOLOGICAL CHANGES COLOCALIZE WITH DEPOSITION OF PrPcJD AND LOSS OF PrPc IN CREU'IZFELDT-JAKOB DISEASE.
Shu-Lian Yang, James A. Mastrianni, and Stephen J.DeArmond*. University of California, School of Medicine, San Francisco ,CA.
Creutzfeldt-Jakob disease (CJD) is clinically and pathologically heterogeneous. Studies of scrapie in animals have shown that neuropathological changes in the brain follow the accumulation of protease resistant PrP, designated PrPsc, and colocalize with it, arguing that accumulation of PrP causes the characteristic neuropathological changes. We are currendy testing whether the neuropathological features in human CJD cases also colocalize with the sites of accumulation of protease resistant PrP, designated PrPcJD, in humans. There are two immunohistochemical methods currendy available to localize PrPcJD: histoblotting of unfixed cryostat sections and hydrolytic autoclaving of formalin-fixed, paraffin-embedded sections. Histoblots are made by pressing a frozen section of brain to nitroceflulose paper, followed by treatment with proteinase K (PK) to eliminate PrPc and with guanidinium to denature PrPcJD and enhance its reactivity with PrP-specific antibodies. Both techniques indicate that PrPcJD accumulation is confined to grey matter. We found, however, a 10% false negative rate with hydrolytic autoclaving and no false negatives by histoblotting. Although more sensitive, histoblots do not reveal the cellular location of PrPcJD nevertheless, three patterns of PrPcJD accumulation have been identified in the cerebral cortex. In 25 cases, PrPcJD was deposited uniformly throughout its full thickness. In 7 cases, PrPcJD accumulated in a laminar pattern in the deeper layers of the cerebral cortex (1ayers V and VI). In 2 cases, staining appeared in a multifocal plaque like pattern in the cerebral cortex. In the absence of PK digestion, the histoblot reveals the location of the normal, non-pathogenic PrP isoform, PrPc. In serial histoblotted sections of CJD brain, the accumulation of PrPcJD was accompanied by the loss of PrPc. These findings suggest that neuronal dysfunction, vacuolation and depletion in prion diseases are due to accumulation of PrPcJD and/or the loss of PrPc. Finally, while hydrolytic autoclaving has failed to demonstrate a precise correlation between the neuropathological changes in CJD and the sites of PrPcJD accumulation, histoblot analysis has shown a strong correlation.
ZR 0
SP englisch
OR Prion-Krankheiten 9