IPA analyses identified CLPP (Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit), RICTOR (rapamycin-insensitive companion of mammalian target of rapamycin), TLE3 (Transducin-like enhancer protein 3), and MMP12 (matrix metalloproteinase protein 12) as the top four Upstream Regulators driving the proteomic changes between AD (low CAA score) vs. aged-matched controls (Figure 5E). The gene discussed is MMP12; the disease is Alzheimer disease.