Pathologic prion protein is specifically recognized in situ by a novel PrP conformational antibody.
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.
Moroncini
Gianluca
G
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
Mangieri
Michela
M
Morbin
Michela
M
Mazzoleni
Giulia
G
Ghetti
Bernardino
B
Gabrielli
Armando
A
Williamson
Robert Anthony
RA
Giaccone
Giorgio
G
Tagliavini
Fabrizio
F
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
D000906:Antibodies; D018620:PrPSc Proteins