CLONING AND CHARACTERIZATION OF THE DROSOPHILA PRESENILIN HOMOLOG

MUTATIONS in two genes, PS1 and PS2, coding for the presenilins, have been linked to the early onset form of familial Alzheimer's disease (A D). Here we report the identification of a Drosophila melanogaster hom ologue of human PS genes, Dps, which maps to band 77B-C on chromosome 3 and is expressed at multiple developmental stages. The predicted ami no acid sequence of the Dps product is 53% identical to human presenil ins, with the greatest similarity in the putative transmembrane domain s, the hydrophobic domains at the beginning and the end of the cytopla smic TM6-TM7 loop and the C-terminus. Analysis of Dps in a genetically tractable model system such as Drosophila may provide insight into th e mechanisms of Alzheimer's disease (AD) necessary for the development of rational therapeutic approaches.