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In prion and Alzheimer's diseases, the roles played by amyloidversus nonamyloid deposits in brain damage remain unresolved.In scrapie-infected transgenic mice expressing prion protein(PrP) lacking the glycosylphosphatidylinositol (GPI) membraneanchor, abnormal protease-resistant PrPres was deposited asamyloid plaques, rather than the usual nonamyloid form of PrPres.Although PrPres amyloid plaques induced brain damage reminiscentof Alzheimer's disease, clinical manifestations were minimal.In contrast, combined expression of anchorless and wild-typePrP produced accelerated clinical scrapie. Thus, the PrP GPIanchor 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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Adriano Aguzzi (3 June 2005) Science308 (5727), 1420.
[DOI: 10.1126/science.1114168] |Summary »|Full Text »|PDF »
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