Our gene-based findings warrant further mechanistic investigations of synergistic benefits that may be brought about by combined treatments with β-secretase inhibitors (e.g., GRL-8234 and TAK-070) [19-21] and feasible therapeutic agents capable of moderately increasing neprilysin expression or activities (e.g., γ-hydroxybutyrate) [65] in animal models relevant to later phases of AD with established Aβ pathology. This evidence concerns the gene MME and Alzheimer disease.