title: Subcellular localization of disease-associated prion protein in the human brain.
abstract: Disease-associated prion protein (PrP(TSE)) 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 PrP(TSE) without damaging epitopes of other antigens, we systematically evaluated co-localization patterns of distinct PrP(TSE) immunodeposits by confocal laser microscopy, including optical serial sectioning. As shown by quantification, the most prominent co-localization of PrP(TSE) is with synaptophysin, but PrP(TSE) may also co-deposit with connexin-32, a gap junction-related protein. Furthermore, neuronal cell bodies, dendrites, axons, astrocytes, and microglia harbor granular PrP(TSE) deposits. Highly aggregated deposits are focally ubiquitinated. We conclude that PrP(TSE) is not exclusively associated with chemical but also with electric synapses, axonal transport may be a relevant route of PrP(TSE) spread in the brain, and activated microglia and astrocytes may play a role in PrP(TSE) processing, degradation, or removal.
authors.affiliation: Institute of Neurology, Medical University of Vienna, AKH 4J, Währinger Gürtel 18-20, POB 48, A-1097 Vienna, Austria.
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Michaela
authors.initials: M
authors.lastname: Strohschneider
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D001921:Brain / Q000473:pathology* / Q000648:ultrastructure; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D017096:Prion Diseases / Q000473:pathology*; D011328:Prions / Q000032:analysis*; D013569:Synapses / Q000473:pathology
chemical_list: D011328:Prions