Effects of human apolipoprotein E isoforms on the amyloid beta-protein concentration and lipid composition in brain low-density membrane domains |
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Authors: | Morishima-Kawashima Maho Han Xianlin Tanimura Yu Hamanaka Hiroki Kobayashi Mariko Sakurai Takashi Yokoyama Minesuke Wada Koji Nukina Nobuyuki Fujita Shinobu C Ihara Yasuo |
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Institution: | Department of Neuropathology, Faculty of Medicine, University of Tokyo, Tokyo, Japan. |
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Abstract: | Apolipoprotein E4 (apoE4) encoded by epsilon 4 allele is a strong genetic risk factor for Alzheimer's disease (AD). ApoE4 carriers have accelerated amyloid beta-protein (A beta) deposition in their brains, which may account for their unusual susceptibility to AD. We hypothesized that the accelerated A beta deposition in the brain of apoE4 carriers is mediated through cholesterol-enriched low-density membrane (LDM) domains. Thus, the concentrations of A beta and various lipids in LDM domains were quantified in the brains of homozygous apoE3 and apoE4 knock-in (KI) mice, and in the brains of those mice bred with beta-amyloid precursor protein (APP) transgenic mice (Tg2576). The A beta 40 and A beta 42 concentrations and the A beta 42 proportions in LDM domains did not differ between apoE3 and apoE4 KI mice up to 18 months of age. The A beta 40 concentration in the LDM domains was slightly, but significantly higher in apoE3/APP mice than in apoE4/APP mice. The lipid composition of LDM domains was modulated in an apoE isoform-specific manner, but its significance for A beta deposition remains unknown. These data show that the apoE isoform-specific effects on the A beta concentration in LDM domains do not occur in KI mouse models. |
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Keywords: | Alzheimer's disease amyloid β-protein apolipoprotein E knock-in mouse lipids low-density membrane domains |
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