Amyloid beta as a regulator of lipid homeostasis

The P-amyloid peptide (AD) is widely considered to be the molecule that causes Alzheimer's disease (AD). Besides this pathological function of AD, recently published data reveal that AD also has an essential physiological role in lipid homeostasis. Cholesterol increases AD production, and conversely AD production causes a decrease in cholesterol synthesis. The latter appears to be mediated by the inhibition of 3-hydroxy-3-methylglutaryi-coenzyme A reductase (HMGR), a key enzyme in cholesterol synthesis, in an action similar to that of statins. Moreover, AD regulates sphingolipid metabolism by directly activating sphingomyelinases (SMases). This review summarizes the molecular basis for the known physiological functions of AD and amyloid precursor protein (APP), the roles of AD and APP in lipid homeostasis and the medical implications of addressing lipid homeostasis in respect to AD. This knowledge might provide new insights for current and future therapeutic approaches to AD.