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Departments of Pathology, Neuropathology Unit (Dr. Jendroska, Ms. Stowring, Mr. Kon, Mr. Stern, and Dr. DeArmond); Medicine (Dr. Heinzel); Neurology (Drs. Torchia, Prusiner, and DeArmond); and Biochemistry and Biophysics (Dr. Prusiner), University of California, San Francisco, CA; and the Institut für Neuropathologie (Dr. Kretzschmar), der Universitä't Miinchen, München, Germany.
Multiple lines of evidence indicate that PrPSc, found only in scrapie, is a necessary component of the infectious scrapie agent. Equally compelling is the evidence that its accumulation in the brain causes the neuropathology characteristic of scrapie. We measured the regional concentration of PrPSc in nine brain regions throughout the course of scrapie in the Syrian hamster following intrathalamic inoculation of prions. PrPSc was compared to the regional concentration of glial fibrillary acidic protein, a measure of reactive astrocytic gliosis. PrPSc was detected first in the thalamus 14 to 21 days postinoculation and next in the septum at 28 days. Initiation of PrPSc synthesis and accumulation in the thalamus was attributable to the inoculum and in the septum to ventricular spread of de novo synthesized PrPSc. The timing and pattern of PrPSc accumulation in all other brain regions suggested transmission along neuroanatomic pathways. Reactive astrocytic gliosis followed PrPSc accumulation in each region by 1 to 2 weeks. Brain PrPSc, determined by summing the concentrations in each brain region, correlated well with scrapie infectivity titers throughout the course of infection (correlation coefficient = 0.975; slope of linear regression line = 1.136). Our results support the hypothesis that PrPSc participates in both the etiology and pathogenesis of prion diseases.
Address correspondence and reprint requests to Dr. Stephen J. DeArmond, Department of Pathology (Neuropathology), Box 0506, University of California, San Francisco, CA 94143.
Supported by research grants from the National Institutes of Health (AG02132 and NS14069) as well as by gifts from National Medical Enterprises and the Sherman Fairchild Foundation. K. Jendroska was supported by Deutsche Forschungsgemeinschaft grant JE145–1.
Received June 14, 1990. Accepted for publication in final form February 20, 1991.
This article has been cited by other articles:
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