PSEN1 and Alzheimer disease: For example, Neprilysin, an Aβ-degrading enzyme of functional relevance to AD that has been previously shown to be transcriptionally downregulated in PSEN1/PSEN2 double knock out fibroblasts and to exhibit reduced activity under chemical (DAPT) inhibition of γ-secretase in mouse neurons [22], was not detected in the current study.