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Science 3 June 2005:
Vol. 308. no. 5727, pp. 1435 - 1439
DOI: 10.1126/science.1110837

Research Articles

Anchorless Prion Protein Results in Infectious Amyloid Disease Without Clinical Scrapie

Bruce Chesebro,1* Matthew Trifilo,2 Richard Race,1 Kimberly Meade-White,1 Chao Teng,2 Rachel LaCasse,1 Lynne Raymond,1 Cynthia Favara,1 Gerald Baron,1 Suzette Priola,1 Byron Caughey,1 Eliezer Masliah,3 Michael Oldstone2

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.

1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, MT 59840, USA.
2 Division of Virology, Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA.
3 Departments of Neurosciences and Pathology, University of California, San Diego, La Jolla, CA 92093, USA.

* To whom correspondence should be addressed. E-mail: bchesebro{at}niaid.nih.gov

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