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: Bruce Chesebro, Matthew Trifilo, Richard Race, Kimberly Meade-White, Chao Teng, Rachel LaCasse, Lynne Raymond, Cynthia Favara, Gerald Baron, Suzette Priola, Byron Caughey, Eliezer Masliah, Michael Oldstone
• Journal: Science (New York, N.Y.) (Science) Vol. 308 Issue 5727 Pg. 1435-9 (Jun 03 2005) ISSN: 1095-9203 [Electronic] United States
• PMID: 15933194 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glycosylphosphatidylinositols
• PrPSc Proteins
• Prions

Topics

• Animals
• Brain (metabolism, pathology, ultrastructure)
• Glycosylphosphatidylinositols (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Plaque, Amyloid (metabolism, pathology)
• PrPSc Proteins (chemistry, metabolism)
• Prion Diseases (etiology, metabolism, pathology)
• Prions (biosynthesis, chemistry, genetics, metabolism)
• Scrapie (etiology, metabolism, pathology)