microRNA-33 Regulates ApoE Lipidation and Amyloid-β Metabolism in the Brain

Brain lipid metabolism, in particular Apolipoprotein E (ApoE) lipidation, is critical to Aβ metabolism and Alzheimer's disease (AD). Brain lipid metabolism is largely separated from the periphery due to blood-brain barrier and different repertoire of lipoproteins. Therefore, identifying the novel regulatory mechanism of brain lipid metabolism may provide a new therapeutic strategy for AD. Although there have been studies on brain lipid metabolism, its regulation, in particular by microRNAs, is relatively unknown. Here, we demonstrate that inhibition of microRNA-33 increases lipidation of brain ApoE and reduces Aβ levels by inducing ABCA1. We provide a unique approach for AD therapeutics to increase ApoE lipidation and reduce Aβ levels via pharmacological inhibition of microRNA in vivo.