TY - JOUR
T1 - Pathologic prion protein is specifically recognized in situ by a novel PrP conformational antibody
AU - Moroncini, Gianluca
AU - Mangieri, Michela
AU - Morbin, Michela
AU - Mazzoleni, Giulia
AU - Ghetti, Bernardino
AU - Gabrielli, Armando
AU - Williamson, Robert Anthony
AU - Giaccone, Giorgio
AU - Tagliavini, Fabrizio
PY - 2006/9
Y1 - 2006/9
N2 - Prion diseases are characterized by the accumulation in the brain of abnormal conformers (PrPSc) of the cellular prion protein (PrPC). PrPSc immunohistochemistry, currently based on antibodies non-distinguishing between PrPC and PrPSc, requires pre-treatments of histological sections to eliminate PrPC and to denature PrPSc. We employed the PrPSc-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 PrPSc deposits was obtained by means of a PrPSc-specific antibody. Such unique reagent may have many applications in the study of prion biology and in the diagnosis and prevention of prion diseases.
AB - Prion diseases are characterized by the accumulation in the brain of abnormal conformers (PrPSc) of the cellular prion protein (PrPC). PrPSc immunohistochemistry, currently based on antibodies non-distinguishing between PrPC and PrPSc, requires pre-treatments of histological sections to eliminate PrPC and to denature PrPSc. We employed the PrPSc-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 PrPSc deposits was obtained by means of a PrPSc-specific antibody. Such unique reagent may have many applications in the study of prion biology and in the diagnosis and prevention of prion diseases.
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U2 - 10.1016/j.nbd.2006.06.008
DO - 10.1016/j.nbd.2006.06.008
M3 - Article
C2 - 16876426
AN - SCOPUS:33747192871
VL - 23
SP - 717
EP - 724
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 3
ER -