title: Anchorless prion protein results in infectious amyloid disease without clinical scrapie.
abstract: In prion and Alzheimer's diseases, the roles played by amyloid versus nonamyloid deposits in brain damage remain unresolved. In scrapie-infected transgenic mice expressing prion protein (PrP) lacking the glycosylphosphatidylinositol (GPI) membrane anchor, abnormal protease-resistant PrPres was deposited as amyloid plaques, rather than the usual nonamyloid form of PrPres. Although PrPres amyloid plaques induced brain damage reminiscent of Alzheimer's disease, clinical manifestations were minimal. In contrast, combined expression of anchorless and wild-type PrP produced accelerated clinical scrapie. Thus, the PrP GPI anchor may play a role in the pathogenesis of prion diseases.
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA. bchesebro@niaid.nih.gov
authors.forename: Bruce
authors.initials: B
authors.lastname: Chesebro
authors.forename: Matthew
authors.initials: M
authors.lastname: Trifilo
authors.forename: Richard
authors.initials: R
authors.lastname: Race
authors.forename: Kimberly
authors.initials: K
authors.lastname: Meade-White
authors.forename: Chao
authors.initials: C
authors.lastname: Teng
authors.forename: Rachel
authors.initials: R
authors.lastname: LaCasse
authors.forename: Lynne
authors.initials: L
authors.lastname: Raymond
authors.forename: Cynthia
authors.initials: C
authors.lastname: Favara
authors.forename: Gerald
authors.initials: G
authors.lastname: Baron
authors.forename: Suzette
authors.initials: S
authors.lastname: Priola
authors.forename: Byron
authors.initials: B
authors.lastname: Caughey
authors.forename: Eliezer
authors.initials: E
authors.lastname: Masliah
authors.forename: Michael
authors.initials: M
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism; D017096:Prion Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012608:Scrapie / Q000209:etiology* / Q000378:metabolism / Q000473:pathology
chemical_list: D017261:Glycosylphosphatidylinositols; D018620:PrPSc Proteins; D011328:Prions