Fig. 3.
Roles of apoE in lipid redistribution among cells in the CNS and apoE isoform-specific differences in neuropathology. ApoE is synthesized by astrocytes, activated microglia, and neurons. Three potential detrimental roles for apoE4: (1) enhanced Aβ production, (2) potentiation of Aβ1–42-induced lysosomal leakage and apoptosis, and (3) enhanced neuron-specific proteolysis resulting in translocation of neurotoxic apoE4 fragments in the cytosol, where they are associated with cytoskeletal disruption and mitochondrial dysfunction.