We also propose that there are three major groups of AD subjects that are initiated either by White Matter Injury (Age, genetics, systemic factors) (Figure 1, arrow 5), Cholesterol dysmetabolism (APOE4, other genes, diet) (Figure 1, arrow 4) or Abeta dysmetabolism (FAD, other genes) (Figure 1, arrow 6). The gene discussed is PSEN1; the disease is Alzheimer disease.