title: Immunohistochemistry for the prion protein: comparison of different monoclonal antibodies in human prion disease subtypes.
abstract: Demonstration of the abnormal form of the prion protein (PrP) in the brain confirms the diagnosis of human prion disease (PrD). Using immunohistochemistry, we have compared ten monoclonal antibodies in PrD subtypes including sporadic and variant Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Alzheimer's disease (AD), and control brains. CJD subgroups were determined using Western blot analysis for the protease-resistant PrP type in combination with sequencing to determine the genotype at the methionine/valine polymorphism at codon 129 of the prion protein gene. None of the antibodies labeled given subgroups exclusively, but the intensity of immunoreactivity varied among morphologically distinct types of deposit. Fine granular or synaptic PrP deposits stained weakly or not at all with antibodies against the N-terminus of PrP, and were visible in one case only with 12F10 and SAF54. Coarser and plaque type deposits were immunolabeled with all antibodies. The immunostaining patterns appear characteristic for the disease subgroups. Labeling of certain neurons in all cases irrespective of disease, and staining at the periphery and/or throughout the senile plaques of AD patients were also noted. Antibodies such as 6H4 and 12F10 failed to give this type of labeling and are therefore less likely to recognise non-pathological PrP material in immunohistochemistry.
authors.affiliation: Institute of Neurology, University of Vienna, and Austrian Reference Centre for Human Prion Diseases.
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
authors.forename: Ivan
authors.initials: I
authors.lastname: Hegyi
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: Bunn
authors.forename: Helga
authors.initials: H
authors.lastname: Flicker
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
authors.forename: Linda
authors.initials: L
authors.lastname: McCardle
authors.forename: Lajos
authors.initials: L
authors.lastname: László
authors.forename: Christa
authors.initials: C
authors.lastname: Jarius
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic / Q000235:genetics / Q000276:immunology; D017096:Prion Diseases / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D011328:Prions / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D011328:Prions; D020033:Protein Isoforms