IPA analyses identified MAPT (microtubule associated protein tau), CLPP (Caseinolytic Mitochondrial Matrix Peptidase Proteolytic Subunit), KDM5A (Lysine-specific demethylase 5A) and APP (amyloid precursor protein) as the top four Upstream Regulators driving the proteomic changes between low vs. high CAA Alzheimer's disease cerebrovascular tissue (Figure 7E). This evidence concerns the gene CLPP and Alzheimer disease.