Anchorless prion protein results in infectious amyloid disease without clinical scrapie.
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.
Chesebro
Bruce
B
Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA. bchesebro@niaid.nih.gov
Trifilo
Matthew
M
Race
Richard
R
Meade-White
Kimberly
K
Teng
Chao
C
LaCasse
Rachel
R
Raymond
Lynne
L
Favara
Cynthia
C
Baron
Gerald
G
Priola
Suzette
S
Caughey
Byron
B
Masliah
Eliezer
E
Oldstone
Michael
M
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
D017261:Glycosylphosphatidylinositols; D018620:PrPSc Proteins; D011328:Prions