Regional difference of lipid distribution in brain of apolipoprotein E deficient mice

According to recent knowledge, apolipoprotein E (apo E) plays a significant role in the homeostasis of intracellular cholesterol level in various tiss ues. Apo E deficient mice develop hyperlipidemia, and suffer from atheroscl erosis in extracerebral blood vessels and neurodegeneration in the central nervous system. Furthermore, Walker et al. (Am. J. Path., 1997;151:1371-137 7) demonstrated cerebral xanthomas of various sizes in the brain of apo E d eficient mice. In the present study, it is illustrated that in the homozygous apo E defici ent mice of advancing age, a great number of foamy macrophages extravasate from microvessels in thalamus and fimbria hippocampi, and scatter in the pe rivascular regions and migrate toward the ependyma, fimbria hippocampi, hip pocampus, and thalamus. Here, it must be pointed out that under hyperlipide mia, although foamy macrophages made dusters in the perivascular region, th e cerebral microvessels did not develop atherosclerosis. On the other hand, in the other cerebral regions such as cerebral cortex, caudoputamen, globu s pallidus, and substantia nigra, macrophages did not appear and microvesse ls retained normal shapes, but the fluorescent granular perithelial (in sho rt, FGP) cells accompanied by these vessels contained a certain amount of l ipids. That is, in the cerebral cortex and caudoputamen, lipid components a re detected in FGP cells and microglia, while in the globus pallidus and su bstantia nigra, they are mainly localized in astrocytes. The reason why the astrocytes in such defined regions contain, specifically, a high quantity of lipid components remains unsettled. Axonal degenerations are often repre sented in thalamus, globus pallidus, and substantia nigra. On the other hand, in the specimens of Wild-type mice, lipid components wer e observed only in FGP cells, and the vascular architecture took a normal p rofile. Any lipid laden macrophages and the axonal degenerations could not be detected through the cerebral parenchyma. Furthermore, it is also a noticeable finding that immunohistochemically, th e FGP cells express a positive reaction against the antibody of apo E in th e Wild-type mice, but those of homozygous apo E deficient mice are immunone gative. FGP cells are not only provided with the scavenger receptor, but al so contribute to the lipid metabolism in the brain. Anat Rec 256:165-176, 1 999. (C) 1999 Wiley-Liss, Inc.