Expressing mRNAs for presenilin-1 and amyloid precursor protein (APP-695) from same neuronal populations in rat hippocampus.

Presenilin-1 gene (PS1, s182) encoding a protein that contains seven transmembrane domains was recently identified as a risk factor for Alzheimer's disease (AD). Mutations on this gene may contribute to pathogenesis of AD. In this study, we used in situ hybridization histochemistry to detect the expression of PS1 in neurons in the hippocampal formation and cerebral cortex of the rat brain. Specifically, mRNAs of PS1 were predominantly found in pyramidal neurons in CA1, CA3, and granule cells in the hilar region of the dentate gyrus of the hippocampus and in the external and internal pyramidal layers of the cerebral cortex. The same neuronal populations express the amyloid protein precursor (APP-695). Transgenic mice expressing a mutated APP-695 produced increased levels of beta-amyloid (A beta) and exhibited behavioral deficits. These results lead us to suggest that when PS1 and APP-695 colocalize in neurons in the brain, PS1 may play a regulatory role in production of (A beta) protein of AD.