ApoE Secretion

Consistent with the localization of its mRNA in vivo and its presence in extracellular sites,81 apoE was shown to be synthesized and secreted in vitro by glial cells, but not by neurons. Astrocytic secretion of apoE was demonstrated in both perinatal rat and fetal human primary cultures.87,88 Confirmation that rat astrocytes synthesize apoE came from electron microscopic immunocytochemical studies which demonstrated the presence of apoE in the Golgi apparatus.81 The same techniques, when applied to the rat optic nerve, also localized apoE in the Golgi apparatus of oligodendrocytes, indicating synthesis by these cells.83 Although apoE secretion by microglia has not been demonstrated, the fact that the corresponding transcripts could be detected in cultured rat microglia suggests that this cell type may represent a possible source of apoE.69,89

Since neurons have not been shown to either secrete apoE or transcribe its corresponding gene, intraneuronal apoE is presumed to reflect cellular uptake, as demonstrated using hippocampal neuronal cell primary cultures.90 The presence in vivo of apoE in CNS neurons was shown by immunoelectron microscopy to be confined to the cytoplasm of cell bodies and proximal dendrites in association with the external membrane surface of some organelles.80 This observation suggests that apoE may affect neuronal metabolism in additional ways not related to cholesterol homeostasis or, alternatively, be involved in the intra-cellular transport of lipids.

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