Apolipoprotein E exerts selective and differential control over vitamin E concentrations in different areas of mammalian brain

Abstract

Apolipoprotein E (apoE) is known to be a risk factor for the incidence of Alzheimer's disease (AD). In addition, vitamin E has been reported to have a role in the treatment of AD. We examined the potential interrelationship between vitamin E and apoE in brain. As the first step, we determined the concentrations of a-tocopherol in selected brain regions of apoE-deficient mice at different ages. The mice were fed normal rodent chow. All regions of the brain in apoE-deficient mice contained less a-tocopherol than control samples at 2.5 months of age, the initial time of study. This trend continued for 9.5 months for most regions except the spinal cord and cerebellum. Tocopherol levels in these latter regions of apoE-deficient animals increased to control levels during the study. Serum a-tocopherol and cholesterol levels were high in the apoE-deficient animals; however, the CNS cholesterol levels were the same in apoE-deficient and control mice. This suggests that 1) the decline in brain a-tocopherol in apoE deficiency is not due to overall alterations in lipid metabolism; and 2) the processing of a-tocopherol in brain follows a separate pathway than that of cholesterol. Subcellular concentrations of a-tocopherol were unaltered by apoE deficiency indicating that intracellular handling of tocopherol is not affected by apoE. ApoE may be an important protein controlling vitamin E levels in specific brain regions. Further understanding of the interactions between apoE and vitamin E could be important in the appropriate use of vitamin E in AD. V V C 2006 Wiley-Liss, Inc.

Mice lacking α-tocopherol transfer protein gene have severe α-tocopherol deficiency in multiple regions of the central nervous system

“…These include genes encoding scavenger receptor B-1 (SR-B1) (Goti et al, 2001;Mardones et al, 2002;Reboul et al, 2006), phosphilipid transfer protein (Desrumaux et al, 1999;Desrumaux et al, 2005;Huuskonen et al, 2001;Jiang et al, 2002), apolipoprotein E (Reich et al, 2001;Vatassery et al, 2006) lipoprotein lipase (Goti et al, 2002) and tocopherol binding proteins (Kempna et al, 2003;Stocker and Azzi, 2000). In this study we assayed the expression of SR-B1 and found it to undetectable in the three brain regions of WT mice (Fig.…”

Transcriptome profiling of equine vitamin E deficient neuroaxonal dystrophy identifies upregulation of liver X receptor target genes

“…The overall goal of this study was to further characterize the degree of α-TOH deficiency in eNAD-affected horses and identify differentially expressed genes and pathways in the central nervous system (CNS) by global transcriptome sequencing. Based on comparative phenotypes across species, we hypothesized that the most relevant pathways would include those related to vitamin E transport or metabolism, which is intimately tied to cholesterol homeostasis based on shared biochemical properties (7). Additionally, vitamin E is the major lipophilic antioxidant to protect against formation of cholesterol oxidation products (oxysterols) that can result in neurodegeneration (8).…”

Brains of apolipoprotein E deficient mice fed vitamin E deficient diets show alteration in handling alpha tocopherol injected into the cerebral ventricles

“…Previous reports from our laboratory showed that the lack of apoE results in lower brain levels of alpha tocopherol [7]. It has also been shown earlier that the uptake and retention of radioactive tocopherol injected into the cerebral ventricles of ApoE-deficient mice was different from wild type animals [8].…”

“…Recently, we reported that apoE deficiency is associated with declines in the steady state concentrations of alpha tocopherol in different regions of mouse brain [7]. The extent of decline in concentration was specific to the anatomic site within the brain and was also dependent on age.…”