Overall, we identify 50 candidate AD risk gene homologs with requirements for CNS structure or function, including 18 whose loss of function causes neurodegeneration (e.g., Snx6/SNX32 and ClC-a/CLCN1), 35 required for neurophysiology (e.g., Arr1/ARRB2, stai/STMN4), and 8 with diminished CNS resilience following a thermal or mechanical stress (e.g., cindr/CD2AP, Amph/BIN1). The gene discussed is ARRB2; the disease is Alzheimer disease.