Mutations in the presenilin (PS) 1 and 2 genes are associated with autosomal dominant Alzheimer disease. PS1 shares striking homology with sel-12, a C. elegans gene implicated in the function of lin-12/Notch, a protein important in neurogenesis. We studied mRNA expression using RT-PCR and in situ hybridization techniques during neural development in mouse and rat. Strong expression of PSs and Notch1 was observed in embryos, especially in the ventricular zone, which decreased gradually as embryos developed. Very low levels of PSs and Notch were present in adulthood, their signals present primarily in the hippocampus and cerebellum. These observations show that, like Notch, PS1 and PS2 are strongly developmentally regulated, and support the plausibility of an interaction between PSs and Notch.