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Division of Psychiatry (Drs. Roberts and Crow, and R. Lofthouse), Clinical Research Centre, Harrow, Middlesex, UK; Department of Biochemistry (Drs. Allsop and Landon), Medical School, Nottingham, UK; Department of Human Morphology (Dr. Kidd), Medical School, Nottingham, UK; and the Departments of Neurology and Biochemistry (Dr. Prusiner), University of California, San Francisco, CA.
The amyloid plaques found in neurodegenerative diseases show considerable morphologic diversity. Two amyloidogenic proteins have been isolated from the brains of humans and animals with neurodegenerative diseases-ß-protein from Alzheimer's disease (AD) and Down's syndrome, and prion protein (PrP) from scrapie and Creutzfeldt-Jakob disease (CJD). Using monoclonal antibodies to a synthetic peptide corresponding to a portion of ß-protein and rabbit antiserum to hamster scrapie PrP 27–30, we examined in situ amyloid plaques on sections from cases of neurodegenerative diseases, including cases with a spectrum of plaque types. Anti-ß-peptide stained cerebrovascular and plaque core amyloid in all AD cases as well as cerebrovascular amyloid and senile plaque core amyloid in five elderly CJD cases. Anti-PrP stained plaques in CJD, kuru, and Gerstmann-Sträussler syndrome cases but not cerebrovascular amyloid or plaques in AD. Dual localization experiments showed that in cases with a mixture of plaque types, the antibodies identified different populations of plaques that showed anatomic heterogeneity. Colocalization of the two proteins was not observed in any plaque type. The data suggest that in neurodegenerative diseases two major plaque types exist, which have different etiologic origins. Our results emphasize the need for classification of CNS amyloids based not on their morphology but on the macromolecular components comprising these pathologic polymers.
Address correspondence to Dr. Prusiner, Department of Neurology, HSE-781, University of California, San Francisco, CA 94143–0518. Address reprint requests to Dr. Roberts, Division of Psychiatry, Clinical Research Centre, Watford Road, Harrow, Middlesex, HA1 3UJ, UK.
Supported by research grants from the National Institutes of Health (AG02132 and NS14069), a Senator Jacob Javits Center of Excellence in Neuroscience grant (NS22786), and a research contract (86-89627) from the California State Department of Health Services, as well as by gifts from Sherman Fairchild Foundation and RJR-Nabisco, Inc.
Received November 6, 1987. Accepted for publication in final form March 18, 1988.
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