APP and Alzheimer disease: The AD-DS, Chr 21 and AD risk factor genesets overlap by eight genes:APP,BACE2,COL18A1,DYRK1A,RCAN1,SOD1,SYNJ1, andS100B (Figure 1).BACE2 encodes an integral membrane glycoprotein that cleaves the APP protein into amyloid-β, a critical step in the cause of AD and DS.COL18A1 encodes the alpha chain of type XVIII collagen.