Apolipoprotein E (apoE), a well characterized protein, forms lipoprotein complexes with cholesterol. Such complexes formed are endocytosed via the LDL receptor family by many cell types in particular within the human central nervous system (CNS). The apoE-endocytic pathway leads to apoE degradation. However, it has recently been indirectly shown that apoE can be retained intracellularly and then re-secreted. To investigate the fate of endocytosed apoE isoforms E2 and E3 within human CNS cells in real-time, we added the CNS form of these apoE isoforms, linked to a green fluorescent protein (EGFP), to cultured human foetal brain tissue. There was bi-directional trafficking of apoE-EGFP in neuron and astrocyte processes and ‘stationary’ perinuclear vesicles in type-I astrocytes. Thus, active apoE recycling in cells with defined processes suggests a role for apoE in mediating signalling through receptor-mediated endocytosis.