EXPRESSION OF PRESENILIN-1 AND PRESENILIN-2 MESSENGER-RNAS IN RAT ANDALZHEIMERS-DISEASE BRAINS

Recently, new genetic linkages have been identified for early-onset fa milial Alzheimer's disease (AD). Mutations have been found in the pres enilin (PS)-1 (S182) gene on chromosome 14 and the PS-2 (STM2/E5-a) ge ne on chromosome 1. We have investigated the distribution of gene expr ession of both presenilins in normal rat brain, and in human control a nd AD cases using in situ hybridization histochemistry. In normal rat brain, intense PS-1 mRNA expression was observed predominantly in neur ons, particularly hippocampal pyramidal and dentate granular neurons a nd cerebellar Purkinje and granular neurons. The distribution of inten sely expressing PS-2 mRNA cells was similar to that of PS-1, but addit ional groups in the brain stem and cortex were identified. Faint but s ignificant mRNA expression of both PS genes was detected in white matt er. In control human cases, the same neuronal cell types as seen in ra t brain expressed both PS mRNAs in the hippocampus and cerebellum. In AD cases, the expression of both mRNAs was markedly decreased in the h ippocampus but not in the cerebellum. In addition, PS-2 hybridization showed increased mRNA expression in astrocyte-like cells in affected a reas of AD cases, The present data indicate that the PS genes may play important roles in specific neurons in normal brain, and that the dec reased expression in neurons in sporadic AD brain may bear some relati onship to the pathogenesis.