Neither experimental knockout of Nrf2 nor transgenic supply of more copies of the gene have provided much useful information about the development of therapies for the prevention or management of cardiovascular disease, stroke, Parkinson’s or Alzheimer’s disease, infectious diseases, etc. The answers will lie in understanding and controlling the perturbations to the networks that underlie all of these diseases. The gene discussed is NFE2L2; the disease is early-onset autosomal dominant Alzheimer disease.