Liver-x Receptor Agonists Modulate Hdl and Amyloid-Beta Metabolism in Brain Capillary Endothelial Cells Forming the Blood-Brain Barrier

Objectives: The overproduction and accumulation of the amyloidogenic product of amyloid precursor protein (APP), amyloid-ß peptide (Aß) in the brain is gaining significant support as the primary causative agent of Alzheimer's disease (AD). Although restricted from entering the brain due to the presence of tight junctions between brain capillary endothelial cells (BCEC), high plasma HDL protect against lipid-related neurodegenerative diseases. Liver-X receptors (LXRs) are nuclear transcription factors regulating HDL metabolism, and LXR agonists decrease the production of Aß. Unlike cholesterol, its brain-specific metabolite and LXR ligand, 24(S)-hydroxycholesterol (24OH-C) is able to readily traverse the BBB.