Suggesting a protective effect of CYP46A1 on cognitive functions in normal aging processes. In spite of the increased levels of synaptic proteins the levels of cholesterol in the brain of the CYP46A1 transgenic mice were not different from those of the controls. Consistent with our previous studies with heterozygotes, evidence showed that the overexpression of CYP46A1 is associated with an increased rate of synthesis of cholesterol. This effect was rather moderate, however the increased synthesis could not be observed at the transcriptional level. Thus, it is tempting to suggest that there may be a relation between cognitive function and flux in the mevalonate pathway not only at a low rate of this flux as shown previously but also at an increased rate of this flux. It is noteworthy that cholesterol synthesis is reduced in Huntingtons disease. The situation in Alzheimers disease is controversial. In AD, it has been shown that b-amyloid reduces cholesterol synthesis but also that increased levels of cholesterol in critical membranes may increase production of b-amyloid. If there is a relation between cognition and rate of brain cholesterol synthesis as suggested by the work by Kotti et al and the present study, this could have clinical implications. For example, inhibition of cholesterol synthesis by statins would not be expected to have a beneficial effect on cognition. Indeed, loss of memory has been reported to be a rare side-effect of treatment with statins. In summary, our results suggest that increased levels of 24OH have beneficial effects on cognition and synaptic plasticity in old female mice. Further work is needed, however, to confirm a relation between cholesterol synthesis in the brain and cognitive function. Diabetic retinopathy is the leading cause of blindness in people of working age. It is caused by oxygen starvation in the retina, which induces glial cell damage and aberrant formation of blood vessels that destroy retinal architecture. Proliferative diabetic retinopathy, the final stage of DR, is characterized by abnormal fibrovascular proliferation and preretinal neovascularization induced by ocular ischemia with subsequent intravitreal hemorrhage and tractional retinal detachment. VEGF has been considered to be the most important mediator of diabetic retinopathy. Although inhibition of VEGF reduces retinal neovascularization, it does not completely inhibit ischemia-driven neovascularization and retinal cell proliferation. Thus, the involvement of other factors in this process seems likely. Apelin is a peptide growth factor that binds the APJ receptor with high affinity. Developmental studies have shown that apelin is highly expressed in many cells in the human body, including endothelium and vascular smooth muscle cells. Moreover, some studies have shown that the apelin ligand is coexpressed with APJ in the developing blood vessels of perinatal mouse retina and glial cells, both in the brain and in the retina.