title: Preclinical detection of infectivity and disease-specific PrP in blood throughout the incubation period of prion disease.
abstract: Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms of the prion protein, PrP. Although cases of clinical vCJD are rare, there is evidence there may be tens of thousands of infectious carriers in the United Kingdom alone. This raises concern about the potential for perpetuation of infection via medical procedures, in particular transfusion of contaminated blood products. Accurate biochemical detection of prion infection is crucial to mitigate risk and we have previously reported a blood assay for vCJD. This assay is sensitive for abnormal PrP conformers at the earliest stages of preclinical prion disease in mice and precedes the maximum infectious titre in blood. Not only does this support the possibility of screening asymptomatic individuals, it will also facilitate the elucidation of the complex relationship that exists between the ensemble of abnormal PrP conformers present in blood and the relationship to infectivity.
authors.affiliation: MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Elizabeth B
authors.initials: EB
authors.lastname: Sawyer
authors.affiliation: MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Julie Ann
authors.initials: JA
authors.lastname: Edgeworth
authors.affiliation: MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Claire
authors.initials: C
authors.lastname: Thomas
authors.affiliation: MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.affiliation: MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D007562:Creutzfeldt-Jakob Syndrome / Q000097:blood; D006403:Hematologic Tests / Q000379:methods; D055256:Infectious Disease Incubation Period; D057230:Limit of Detection; D008163:Luminescent Measurements / Q000379:methods; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008647:Mesocricetus; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000097:blood*; D011328:Prions / Q000097:blood*
chemical_list: D011328:Prions; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse