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PRESENILIN-1 (PS1) and presenilin-2 (PS2) are associated with a majority of early onset familial Alzheimer's disease (FAD). Sequence analysis of PS1/2 has revealed integral transmembrane proteins which are highly homologous to the protein coded by sel-12, a Caenorhabditis elegans gene involved in the lin-12/Notch signaling pathway. The normal function of PS1/2, as well as the pathogenesis caused by mutations of these genes in FAD, are unknown however. We have identified a Drosophila presenilin homolog (DPS) and mapped the chromosomal location of this gene. DPS shows 53% amino acid identity to PS1/2 and 45% to the sel-12 product. Strong amino acid conservations appear at the position associated with FAD. In embryonic stages, DPS is expressed primarily in the CNS.