Figure 1

Mechanisms of amyloid beta (Aβ) clearance are mediated by apolipoprotein E (ApoE) and ATP-binding cassette A1 (ABCA1). Activation of nuclear hormone receptors - liver × receptor (LXR), peroxisome proliferator-activated receptor gamma (PPARγ), and retinoid × receptor (RXR) - induces the expression of ApoE and ABCA1. The lipidation of ApoE by ABCA1 stimulates the degradation of Aβ through multiple pathways: extracellular degradation by insulin-degrading enzyme (IDE) or uptake by microglial cells and subsequent lysosomal degradation. Aβ can also be cleared from the central nervous system by binding to ApoE receptors such as low-density lipoprotein receptor (LDLR) or LDLR-related protein 1 (LRP1) that mediate transport across the blood-brain barrier.