NR ARLM
AU Kovacs,G.G.; Preusser,M.; Strohschneider,M.; Budka,H.
TI Subcellular localization of disease-associated prion protein in the human brain
QU American Journal of Pathology 2005 Jan; 166(1): 287-94
PT journal article
AB Disease-associated prion protein (PrPtse) deposits in distinct immunostaining patterns in the brain in Creutzfeldt-Jakob disease, including synaptic, extracellular, and cell-associated localizations. After having developed an appropriate pretreatment protocol to enhance immunostaining for PrPtse without damaging epitopes of other antigens, we systematically evaluated co-localization patterns of distinct PrPtse immunodeposits by confocal laser microscopy, including optical serial sectioning. As shown by quantification, the most prominent co-localization of PrPtse is with synaptophysin, but PrPtse may also co-deposit with connexin-32, a gap junction-related protein. Furthermore, neuronal cell bodies, dendrites, axons, astrocytes, and microglia harbor granular PrPtse deposits. Highly aggregated deposits are focally ubiquitinated. We conclude that PrPtse is not exclusively associated with chemical but also with electric synapses, axonal transport may be a relevant route of PrPtse spread in the brain, and activated microglia and astrocytes may play a role in PrPtse processing, degradation, or removal.
AD Institute of Neurology, Medical University of Vienna, AKH 4J, Wahringer Gürtel 18-20, POB 48, A-1097 Vienna, Austria.
SP englisch
PO USA