We have recently constructed a cDNA library from the brain mRNAs of animals infected with the scrapie agent. Using differential screening and in situ hybridization we have found a cDNA clone to a gene whose expression increases in scrapie. This cloned DNA probe binds to cells in the brains of infected animals, to the senile plaques in Alzheimer's dementia (AD), and to cells in the brain tissues from elderly patients. We propose to continue the analysis of this clone and others in the library in order to gain insight into the nature of the scrapie agent and the origins of pathological alterations in the aging brain that occur in scrapie and AD. We also plan a more direct approach in the pathology of AD using the same strategy of differential screening of a library from the mRNAs of AD, to find genes whose ativity is increased in the aging brain and genes which by in situ hybridization have the appropriate tissue and cellular localization to suggestive involvement in the pathological process.
| Diedrich, J F; Minnigan, H; Carp, R I et al. (1991) Neuropathological changes in scrapie and Alzheimer's disease are associated with increased expression of apolipoprotein E and cathepsin D in astrocytes. J Virol 65:4759-68 |
