Diagram of the potential molecular mechanisms. The combination of aging and ApoE deficiency is associated with an increase of arginase activity with no changes in eNOS. Higher arginase activity would lead to a decrease of NO availability caused by a depletion of L-arginine. One of the possible consequences would be a decrease in blood brain perfusion and facilitated lipid deposition around the microvessels. The increase of arginase activity could also contribute to an increase of urea and induce changes in the NVU homeostasis. The changes in the NVU and neuroinflammation, characterized by the opening of the BBB and increase of GFAP and AQP4 expression, might be a consequence of the decrease of NO, decrease of blood brain perfusion, and increase of urea.