Apolipoprotein E Immunolocalization

The distribution of apoE immunoreactivity in the brain of mammals was shown to vary from one species to the other. In addition, cell type labeling within a given species has also been found to vary between studies. This variation has been attributed to differences in the protocols used, mainly with regard to tissue fixation procedures and reactivity of the apoE antiserum.80 In general, neurons stain rather poorly while astrocytes represent the glial cell type most consistently immunopositive. Astrocytes were labeled in the perinuclear region, as well as their processes that terminated on blood vessels and the pial surface.78,81

In rats and mice, apoE immunoreactivity has been shown in a variety of cell types including some fibrous and protoplasmic astrocytes, microglia, ependymocytes, and in the epithelia lining the choroid plexus.78,81,82 With regard to specialized astrocytic cells such as Bergmann glia, one study showed positive staining for apoE (as well as in tanycytes)81 while another did not.82 In most cases, no apoE immunoreactivity was observed in oligodendro-cytes identified by morphological and topographic criteria. However, in a study that focused on the normal mature optic nerve both astrocytes and oligodendrocytes were apoE-positive, using specific glial markers.83 Rodent neurons are usually not immunoreactive, but faint staining has been observed in occasional neurons in adult rats and mice.78,82

In primates, apoE immunoreactivity was observed in astrocytes (in both white and gray matter), ependymocytes, microglia (in older specimens), as well as in neurons, where it is common even in young animals.82 Most neuronal staining was faint and perinuclear, but intense labeling of both distal dendrites and axonal processes was often seen in cortical and, especially, in hippocampal CA1-2 pyramidal neurons.82 In contrast, granule neurons in the dentate gyrus were mostly unstained. In prosimians, the density of apoE-immunoreactive neurons generally increased with age.82

Intraneuronal localization of apoE has also been reported in several studies that examined human brain specimens. The occurrence of apoE in cortical and hippocampal neurons without neurofibrillary changes was demonstrated in brains of nondemented elderly indi-viduals.84,85 As seen in primates, numerous apoE-immunoreactive neurons were found in the CA1-2 subfields of the hippocampal formation, whereas the granule cell layer did not stain.84 ApoE ICC also revealed staining of hippocampal glial cells (astrocytes and ependy-mal cells), although the intensity varied widely between cases.84 In the frontal cortex, apoE immunoreactivity was intense in some neuronal cell bodies and their processes.85 Most of these cells have been identified as small pyramidal neurons in layer III and some as large pyramidal cells in layer V, using double staining with a second antibody to the neuronal marker microtubule associated protein 2. In this brain region, only a few cells with astrocytic morphology were apoE-positive.85 In contrast, in a single case study from a 34 year old individual who died of pneumonia, apoE was found in all major brain subdivisions exclusively in GFAP-positive astrocytes.86 Together these results indicate that neuronal labeling in humans appears with increasing age. Alternatively, optimal sensitivity of the ICC method used in the last study may not have been reached, thereby not allowing for the detection of lower amounts of apoE in neurons. In this regard, it is of note that in a different study, apoE immunoreactivity in temporal cortex neurons from young patients with epilepsy (21-55 years) was found to be less intense than in astrocytes.80

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