Apolipoprotein D in the Niemann-Pick type C disease mouse brain: an ultrastructural immunocytochemical analysis.

Enhanced apoD gene expression and abnormally high levels of apoD protein accumulation in the brain have been previously documented as features of the neurodegenerative disorder, Niemann-Pick Type C disease (NP-C). In the present study we have used immunocytochemistry and light and electron microscopy to elucidate the cellular and subcellular distribution of apoD in the Balb/c NIH npc1(-/-) mouse brain. The normal mouse brain demonstrates low levels of apoD-expressing glia particularly in the cerebellar white matter. In contrast, abundant, strongly apoD-immunolabeled cells were observed in select grey matter nuclei, including the globus pallidus, thalamus, and substantia nigra, and in white matter tracts within the internal capsule and cerebellum of NP-C mouse brain. These brains regions have been previously shown to display the most significant neurodegenerative changes in the NP-C mouse. Ultrastructural analysis revealed dense apoD immunoreactivity on the nuclear envelopes of cells that have the morphological features of oligodendrocyte precursor-like cells and light staining on astrocytes. These results define the cellular and subcellular pattern of expression of apoD in NP-C mouse brain and suggest a possible role for this lipocalin in the pathophysiology of this disorder.