Apolipoprotein E

Moundras, C. Behr, S.R. Demigne, G. Mazur, A. Remesy, G. (1994). Fermentable polysaccharides that enhance fecal bile acid excretion lower plasma cholesterol and apolipoprotein E-rich HDL in rats. Journal of Nutrition, Vol. 124, No.ll, (November 1994), pp. 2179-2188, ISSN 0022-3166. 

Figure 25-3. Metabolic fate of chylomicrons. (A, apolipoprotein A B-48, apolipoprotein B-48 , apolipoprotein C E, apolipoprotein E HDL, high-density lipoprotein TG, triacylgiycerol C, cholesterol and cholesteryl ester P, phospholipid HL, hepatic lipase LRP, LDL receptor-reiated protein.) Only the predominant lipids are shown.

One of the most likely risk factors for AzD is the patient s genotype for apolipoprotein E (ApoE), which is believed normally to be involved in neuronal repair and growth, but is also found in plaques and tangles. Three distinct forms of ApoE, E2, E3 and E4 are encoded on chromosome 19 but it is the ApoE, E4 allele that occurs at a much higher frequency in late-onset AzD patients (50%) compared with controls (16%) and binds to and possibly increases the formation of )S-amyloid. Many early-onset cases... 

HAYEK T, FURHMAN B, VAYA J, ROSENBLAT M, BELINRY P, COLEMAN R, ELIS A, AVIRAM M (1997) Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consiunption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation aggregation, Arteriosclerosis, Thrombosis and Vascular Biology, 17, 2744-52. 

Fig. 9-4). Very low-density lipoprotein particles are released into the circulation where they acquire apolipoprotein E and apolipoprotein C-II from HDL. Very-low density lipoprotein loses its triglyceride content through the interaction with LPL to form VLDL remnant and IDL. Intermediate-density lipoprotein can be cleared from the circulation by hepatic LDL receptors or further converted to LDL (by further depletion of triglycerides) through the action of hepatic lipases (HL). Approximately 50% of IDL is converted to LDL. Low-density lipoprotein particles are cleared from the circulation primarily by hepatic LDL receptors by interaction with apolipoprotein B-100. They can also be taken up by extra-hepatic tissues or enter the arterial wall, contributing to atherogenesis.4,6... 

The genetic basis for the more common late-onset AD appears more complex. Genetic susceptibility is more sporadic and it may be more dependent on environmental factors.9 The apolipoprotein E (apo E) gene on chromosome 19 has been identified as a strong risk factor for late-onset AD. There are three variants of apo E however, carriers of two or more of the apo E4 allele have an earlier onset of AD (approximately 6 years earlier) compared with non-carriers.9 Only 50% of AD patients have the apo E4 allele, thus indicating it is only a susceptibility marker. 

Apo E, apolipoprotein E CAD, coronary artery disease FKN, fractalkine MHC, major histocompatibility complex MCP-1, monocyte chemoattractant protein 1 MMPs, matrix metalloproteinases NK, natural killer oxLDL, oxidized LDL RANTES, regulated on activation, normal T cell expressed and secreted VSMCs, vascular smooth muscle cells. 

Bea F, Blessing E, Shelley MI, Shultz JM, Rosenfeld ME. Simvastatin inhibits expression of tissue factor in advanced atherosclerotic lesions of apolipoprotein E deficient mice independently of lipid lowering potential role of simvastatin-mediated inhibition of Egr-1 expression and activation. Atherosclerosis 2003 167(2) 187-194. 

Meir KS, Leitersdorf E. Atherosclerosis in the apolipoprotein E-deficient mouse—a decade of progress. Arterioscler Thromb Vase Biol 2004 24(6) 1006-1014. 

Seo HS, Lombardi DM, Polinsky P, et al. Peripheral vascular stenosis in apolipoprotein E-deficient mice—potential roles of lipid deposition, medial atrophy, and adventitial inflammation. Arterioscler Thromb Vase Biol 1997 17(12) 3593—3601. 

Aiello RJ, Bourassa PA, Lindsey S, et al. Monocyte chemoattractant protein-1 accelerates atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vase Biol 1999 19(6) 1518-1525. 

Dawson TC, Kuziel WA, Osahar TA, Maeda N. Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 1999 143(1) 205—211. 

Combadiere C, Potteaux S, Gao JL, et al. Decreased atherosclerotic lesion formation in CX3CRl/apolipoprotein E double knockout mice. Circulation 2003 107(7) 1009-1016. 

Ni W, Egashira K, Kitamoto S, et al. New anti-monocyte chemoattractant protein-1 gene therapy attenuates atherosclerosis in apolipoprotein E-knockout mice. Circulation 2001 103(16) 2096-2101. 

Evans KC, Berger EP, Cho CG, Weisgraber KH, Lansbury PT Jr. Apolipoprotein E is a kinetic but not a thermodynamic of amyloid formation implications for the pathogenesis and treatment of Alzheimer disease. Proc Natl Acad Sci USA 1995 92 763-767. 

Anderson, DH, Ozaki, S, Nealon, M, Neitz, J, Mullins, RF, Hageman, GS, and Johnson, LV, 2001. Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium implications for the process of drusen formation. Am J Ophthalmol 131, 767-781. 

Browning, PJ, Roberts, DD, Zabrenetzky, V, Bryant, J, Kaplan, M, Washington, RH, Panet, A, Gallo, RC, and Vogel, T, 1994. Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi s sarcoma-like lesions in BALB/c nu/nu mice. J Exp Med 180, 1949-1954. 

Bultel-Brienne, S, Lestavel, S, Pilon, A, Laffont, I, Tailleux, A, Fruchart, JC, Siest, G, and Clavey, V, 2002. Lipid free apolipoprotein E binds to the class B type I scavenger receptor I (SR-BI) and enhances cholesteryl ester uptake from hpoproteins. J Biol Chem 277, 36092-36099. 

Ishida, BY, Bailey, KR, Duncan, KG, Chalkley, RJ, Burlingame, AL, Kane, JP, and Schwartz, DM, 2004. Regulated expression of apolipoprotein E by human retinal pigment epithelial cells. J Lipid Res 45, 263-271. 

Kelly, ME, Clay, MA, Mistry, MJ, Hsieh-Li, HM, and Harmony, JA, 1994. Apolipoprotein E inhibition of proliferation of mitogen-activated T lymphocytes Production of interleukin 2 with reduced biological activity. Cell Immunol 159, 124—139. 

Tangirala, RK, Pratico, D, FitzGerald, GA, Chun, S, Tsukamoto, K, Maugeais, C, Usher, DC, Pure, E, and Rader, DJ, 2001. Reduction of isoprostanes and regression of advanced atherosclerosis by apolipoprotein E. J Biol Chem 276, 261-266. 

Thakkinstian, A, Bowe, S, McEvoy, M, Smith, W, and Attia, J, 2006. Association between apolipoprotein E polymorphisms and age-related macular degeneration A HuGE review and meta-analysis. Am J... 

Von Eckardstein, A, Langer, C, Engel, T, Schaukal, I, Cignarella, A, Reinhardt, J, Lorkowski, S, Li, Z, Zhou, X, Cullen, P, and Assmann, G, 2001. ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages. FASEB J 15, 1555-1561. 

Al = aluminium ApoE = apolipoprotein E APP = amyloid precursor protein. 

In 1993/1994 a series of publications caused a stir in the AD research community, since for the first time they linked a specific neuropathological process in late-onset AD to a genetic marker. Researchers looking at the composition of plaques found that the protein apolipoprotein E (ApoE) was associated with p-amyloid in the cerebrospinal fluid (CSF) of AD patients (Strittmatter et al., 1993). The gene for ApoE is on the same human chromosome (number 19) which was a risk factor in some AD pedigrees. The gene for ApoE comes in three versions (alleles) Apo s2, Apo s3 and, most importantly, Apo s4 these result in three slightly different variants of the protein. Humans carry two versions of the allele and so can have none, one or two of any of the versions of the Apo... 

Apolipoprotein E (ApoE) A protein involved in cholesterol transport that has three major isoforms, one of which, ApoE4, significantly increases the risk of developing Alzheimer s disease. 

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL and Pericak-Vance MA (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer s disease in late onset families. Science, 261, 921-923. 

Saunders AM, Strittmatter WJ, Schmechel D, George-Hyslop PH, Pericak-Vance MA, Joo SH, Rosi BL, Gusella JF, Crapper-MacLachlan DR, Alberts MJ et al. (1993). Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer s disease. Neurology, 43, 1467-1472. 

Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS and Roses AD (1993). Apolipoprotein E High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proceedings of the National Academy of Science USA, 90, 1977-1981. 

Rigaud AS, Traykov L, Caputo L, Guel-fi MC, Latour F, Couderc R et al. The apolipoprotein E epsilon4 allele and the response to tacrine therapy in Alzheimer s disease. Eur J Neurol 2000 7 255— 258. 

Apolipoprotein E (APOE) Cholinesterase inhibitor (Tacrine) Susceptibility to Alzheimer s disease, increased by the epsilon-4 allele, and decreased by epsilon-2 allele (91)... 

Bickeboller H, Campion D, Brice A, Amouyel P, Hannequin D, Didierjean O et al. Apolipoprotein E and Alzheimer disease genotype-specific risks by age and sex. Am J Hum Genet 1997 ... 

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