Identifying and Mapping Changes in Gene Expression Involved in the Neuropathology of Scrapie and Alzheimer’s Disease

Abstract

The pathological hallmarks of scrapie are astrogliosis, vacuolation, and, in some combinations of strains of agent and host, neuritic plaques with amyloid cores which resemble those in senile dementia of the Alzheimer type in man (Fraser 1976; Wisniewski et al. 1975). While the nature of the amyloid differs in scrapie and Alzheimer’s disease (AD) (Prusiner et al. 1983; Masters et al. 1985), the analogous pathological lesions of neuritic plaques and astrogliosis in scrapie and AD could imply convergent pathogenetic mechanisms. We have set out to determine not only if this general concept can be substantiated, but, more specifically, whether changes in expression of certain genes form the molecular basis for the neuropathological alterations in both conditions (Wietgrefe et al. 1985; Diedrich et al. 1987; Haase et al. 1986; Duguid et al. 1988, 1989). This chapter begins with an elaboration of the logic underlying this hypothesis, followed by a description of the methods of differential and subtractive screening of cDNA libraries appropriate to testing the tenets of the theory. We conclude with an account of what has already been learned using this approach to understanding the molecular basis of these neuropathological processes.

This work was supported by the National Institutes of Health, Veterans Administration, The American Parkinson Disease Association, Whitaker Health Sciences Fund, and the Graduate School of the University of Minnesota.