Proposed dual role of LRP in Aβ metabolism. Association of Aβ with LRP ligands (apoE, α2M*, or lactoferrin) results in rapid LRP-mediated endocytosis of the complex. On the other hand, association of APP isoforms containing KPI domains (APP_KPI) leads to increased Aβ generation and deposition. In AD, the catabolic pathway may be impaired by decreased levels of LRP at clearance sites (perhaps neurons or sites along the capillary membranes), while Aβ generation may be enhanced by upregulation of LRP in activated glia found in the AD brain.