The LXR agonist GW3965 increases apoA-I protein levels in the central nervous system independent of ABCA1

► ApoA-I is present in the CNS and influences cognitive function. ► ABCA1 deficiency reduces apoA-I levels more extensively in plasma than in the CNS. ► GW3965 treatment elevates apoA-I levels in the CNS independent of ABCA1. ► ApoA-I may be regulated by to distinct pathways in peripheral and CNS compartments. ► ApoA-I may be a point of integration between peripheral and CNS lipid metabolism.