ApoE gene

Fig. 10.13 Potential pleiotropic effects of the apoUpoprotein E (APOE) gene and its products...

For many years, alterations in APOE and defects in the APOE gene have been associated with dysfunctions in lipid metabolism, cardiovascular disease, and atherosclerosis. During the past 25 years, an enormous amount of studies clearly documented the role of APOE-4 as a risk factor for AD, and the accumulation of the APOE-4 allele has been reported as a risk factor for other forms of dementia and CNS disorders (1,12,18-20,47.488). 

Hagberg, J.M., Wilund, K.R., Ferrell, R.E. (2000) APOE gene and gene-environment effects on plasma lipoprotein-lipid levels. Physiol. Genomics, 4, 101-108. 

Familial dysbetalipoproteinemia (type III) is characterized by the accumulation of chylomicron and VLDL remnants, which are enriched in cholesterol compared to their precursors. The primary molecular cause of familial dysbetalipoproteinemia (type III) is the homozygous presence of the apolipoprotein E2 (apoE2) isoform, which is associated with recessive inheritance of the disorder [62]. However, only 1 in 50 homozygotes for apoE2 will develop type III hyperlipoproteinemia, which is clinically characterized by palmar and tuberous xanthomas, arcus lipoides, and premature atherosclerosis of coronary, peripheral, and cerebral arteries. Precipitating factors include diabetes mellitus, renal disease, hemochromatosis, but also familial hypercholesterolemia. In addition, some rare mutations in the apoE gene have been found to cause dominant and more penetrant forms of type III hyperlipoproteinemia. 

Until 1993 apolipoprotein E was best known for its central role in plasma lipoproteins and cholesterol transport (Fig. 21-1). However, one of the three common alleles of the apoE gene confers a significant risk of development of Alzheimer disease.12171218 A high blood cholesterol level is also correlated with increased risk.12191220 Membrane abnormalities in mitochondria have been associated with Alzheimer disease.1221 Also related to membranes and lipid metabolism, vitamin E appears to combat Alzheimer disease.843 1218... 

Harris ID, Evans V, Owen JS. 2006. ApoE gene therapy to treat hyperlipidemia and atherosclerosis. Curr Opin Mol Ther. 8 275-287. 

APOE has three common isoforms, namely, E2, E3, and E4, which are coded by the APOE alleles e2, e3, and e4 at a single locus on chromosome 19. The APOE gene has been extensively examined in populations worldwide for its association with an increased risk for CAD and AD [25, 34] and has also been evaluated in centenarian populations in different studies. 

Palmiter RD, Cole TB, Findley SD (1996) ZnT-2, a mammalian protein that confers resistance to zinc by facilitating vesicular sequestration. EMBO J 15 1784-1791 Peila R, Rodriguez BE, Launer LJ (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies The Honolulu-Asia Aging Study. Diabetes 51 ... 

Lendvirus vectors have also been used in the development of potendal AD therapeudcs. Dodart and colleagues recently delivered varying alleles of the apohpoprotein E (apoE) gene,... 

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