Response to Correspondence: Pardossi-Piquard et al., “Presenilin-Dependent Transcriptional Control of the Aβ-Degrading Enzyme Neprilysin by Intracellular Domains of βAPP and APLP.” Neuron 46, 541–554

We recently established that neprilysin (NEP), one of the putative amyloid β-peptide (Aβ)-degrading enzymes, is transcriptionally upregulated by AICDs, the C-terminal fragments of the β-amyloid precursor protein (βAPP/APLP) that are generated by presenilin (PS)-dependent γ- and ɛ-secretase activities (Pardossi-Piquard et al., 2005). Chen and Selkoe now report lack of evidence of NEP upregulation by PS-dependent γ-secretase. To explore the reasons for this difference, we have repeated several experiments, conducted new experiments, and carefully examined the data presented by Chen and Selkoe.