A) Lipidated ApoE is secreted primarily by astrocytes in the CNS.
B) Microglia secrete ApoE in disease conditions and microglial ApoE can be integrated into existing amyloid-β plaques.
C) ApoE is uptaken by LDLR present on astrocytes and other cell types, such as endothelial cells (see D) and neurons (see E).
D) Amyloid-β and lipidated ApoE may compete for clearance by binding to LDLR receptors. ApoE might also form complexes with amyloid-β which may promote clearance of amyloid-β.
E) ApoE is uptaken by neurons through receptors such as LDLR, LRP1, and HSPG.
F) Recycling endosomes or lysosomes in neurons are potential sites where non-lipidated or partially lipidated ApoE interacts with amyloid-β inducing amyloid-β fibrilization.
G) ApoE in plaques is presumably required for microglial clustering around amyloid-β plaques.
H) ApoE may promote the engulfment of dying or damaged synapses/neurons with fibrillar tau accumulation.