Transcripts for apoE have been shown to be distributed throughout all regions of the brain by RNA dot blot hybridization,62 and have been localized by in situ hybridization to glial cells (astrocytes, ependymocytes and microglia) but not in neurons.65,69,78,79 In the adult mouse brain, there was abundant expression of apoE mRNA in the choroid plexus and ependyma in one study79 but apparently absence of labeling in another (data was not shown).78 High amounts of apoE mRNA were also detected in the medial and lateral habenular nuclei, in several thalamic nuclei as well as in the entire hypothalamus, with somewhat higher grain densities in the latter.79 As described above, these structures also contain high levels of clusterin mRNA in the adult rat. With the obvious exception of the ependymal epithelia, it is not known whether the two transcripts colocalize in the same cell populations.
ApoE transcripts were distributed over the mouse hippocampus and dentate gyrus but, unlike clusterin mRNA, not in their pyramidal and granular layers, respectively, with the highest levels of apoE mRNA seen in the molecular layer of the dentate gyrus.79 These results are consistent with those of two other studies in rats using in situ hybridization in combination with ICC for GFAP and either ED1 or OX42, two different markers for microglia. These latter studies identified astrocytes as the major apoE message-containing cells in the hippocampal formation, but some positive microglial cells could be identified in the CA1 region.65,69 Microglia in the arcuate nucleus of the hypothalamus was also shown to contain apoE transcripts.69
In the cerebral cortex, the apoE message was detected mainly in the outer layers, presumably in astrocytes,79 thereby contrasting with the more ubiquitous expression noted for clusterin transcripts. apoE mRNA-positive cells were also observed in white matter areas in rodent brains, as it was the case for clusterin mRNA.26,65,79 For most of the brain regions, identification of the cell types expressing apoE mRNA would have required ICC for specific glial markers.
ApoE transcripts were also mapped in the cortex of aged humans by in situ hybridization and shown to be present in astrocytes only.78 The distribution and cell type specificity of apoE expression in other regions of the human brain have not been reported.
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