Ceramide and cholesterol: possible connections between normal aging of the brain and Alzheimer's disease. Just hypotheses or molecular pathways to be identified?

Even though it is known that aging is the single most important risk factor for Alzheimer's disease (AD), there is a lack of information on the molecular pathway(s) that connect normal aging of the brain to this form of neuropathology. Because of the rise in average lifespan, the number of individuals that reach the seventh or eighth decade of life and become at high risk for AD is rapidly increasing. Current estimations predict that by 2050 about 45 to 50 million individuals will be affected by AD worldwide. Here, we discuss the need for more age-directed research to understand AD neuropathology. We also elaborate on the possible role of cholesterol and ceramide as molecular connections between aging and AD, and as novel therapeutic targets for the prevention of late-onset AD.