Presenilins encode highly conserved proteins that function as catalytic components of the gamma-secretase complex. Loss-of-function mutations in Presenilin cause a lethal phenotype during development, while missense mutations cause familial Alzheimer's disease in adults. To investigate the role of Presenilins in adults, the effect of conditional loss-of-function mutations in Drosophila presenilin (psn) on oogenesis, learning and memory was investigated in adult wild-type flies using a potent gamma-secretase inhibitor, DAPT. Contrary to the recent evidence that Presenilins play an important role in memory, DAPT-treated flies had no detectable memory impairments. Lack of memory impairments in DAPT-treated flies correlated with a failure of DAPT to inhibit Psn activity in the brain, while the same concentration of DAPT had a strong effect in ovaries. Although, the role of Psn in learning and memory cannot be determined due to failure of DAPT to inhibit Psn activity in the brain, a potential regulatory difference in Notch signal transduction between adult brain and body was identified.