title: Pathologic prion protein is specifically recognized in situ by a novel PrP conformational antibody.
abstract: Prion diseases are characterized by the accumulation in the brain of abnormal conformers (PrP(Sc)) of the cellular prion protein (PrP(C)). PrP(Sc) immunohistochemistry, currently based on antibodies non-distinguishing between PrP(C) and PrP(Sc), requires pre-treatments of histological sections to eliminate PrP(C) and to denature PrP(Sc). We employed the PrP(Sc)-specific antibody 89-112 PrP motif-grafted IgG on mildly fixed, untreated brain sections from several cases of human prion diseases. The results confirmed specific binding of IgG 89-112 to a structural determinant found exclusively on native disease-associated PrP conformations and lost following tissue denaturation or cross-linking fixation. Importantly, IgG 89-112 demonstrated no reactivity with normal brain tissue or with amyloid deposits in Alzheimer disease brain sections. Thus, immunohistochemical detection of native PrP(Sc) deposits was obtained by means of a PrP(Sc)-specific antibody. Such unique reagent may have many applications in the study of prion biology and in the diagnosis and prevention of prion diseases.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Sezione di Clinica Medica, Università Politecnica delle Marche, Polo Didattico, Via Tronto 10, 60020 Ancona, Italy. g.moroncini@univpm.it
authors.forename: Gianluca
authors.initials: G
authors.lastname: Moroncini
authors.forename: Michela
authors.initials: M
authors.lastname: Mangieri
authors.forename: Michela
authors.initials: M
authors.lastname: Morbin
authors.forename: Giulia
authors.initials: G
authors.lastname: Mazzoleni
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Armando
authors.initials: A
authors.lastname: Gabrielli
authors.forename: Robert Anthony
authors.initials: RA
authors.lastname: Williamson
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giaccone
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000906:Antibodies / Q000737:chemistry / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D016477:Artifacts; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D003429:Cross Reactions / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods* / Q000639:trends; D058225:Plaque, Amyloid / Q000276:immunology; D018620:PrPSc Proteins / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D011237:Predictive Value of Tests; D017096:Prion Diseases / Q000175:diagnosis* / Q000276:immunology / Q000503:physiopathology; D011487:Protein Conformation
chemical_list: D000906:Antibodies; D018620:PrPSc Proteins