If our proposed scenario is true, fine control of cortical (but not white matter) myelination in association with proper APP processing in oligodendrocyte lineage cells in aged brains would be one of the essential requirements of effective AD therapy (Supplementary Fig. 14C); however, the exact roles of APP in aOPCs or Aβs secretion, as well as its processing in oligodendrocyte differentiation remain completely unknown. This evidence concerns the gene DDX41 and Alzheimer disease.