APOE and Alzheimer disease: First is an increase in Apoe and downregulation of homeostatic genes such as Purinergic Receptor P2Y12 (P2ry12), followed by an upregulation of Trem2. This DAM phenotype has helped bring together ApoE and TREM2 through a disease specific pathway as well as how mulitple risk factors for AD play a role in this cascade (131, 134).