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Apolipoprotein E (ApoE) is a class of apolipoprotein found in the chylomicron and Intermediate-density lipoprotein (IDLs) that is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.^[1] In peripheral tissues, ApoE is primarily produced by the liver and macrophages, and mediates cholesterol metabolism in an isoform-dependent manner. In the central nervous system, ApoE is mainly produced by astrocytes, and transports cholesterol to neurons via ApoE receptors, which are members of the low density lipoprotein receptor gene family.

Function

APOE ^[2] is 299 amino acids long and transports lipoproteins, fat-soluble vitamins, and cholesterol into the lymph system and then into the blood. It is synthesized principally in the liver, but has also been found in other tissues such as the brain, kidneys, and spleen. In the nervous system, non-neuronal cell types, most notably astroglia and microglia, are the primary producers of APOE, while neurons preferentially express the receptors for APOE. There are seven currently identified mammalian receptors for APOE which belong to the evolutionarily conserved low density lipoprotein receptor gene family.

APOE was initially recognized for its importance in lipoprotein metabolism and cardiovascular disease. Defects in APOE result in familial dysbetalipoproteinemia aka type III hyperlipoproteinemia (HLP III), in which increased plasma cholesterol and triglycerides are the consequence of impaired clearance of chylomicron, VLDL and LDL remnants^{[citation needed]}. More recently, it has been studied for its role in several biological processes not directly related to lipoprotein transport, including Alzheimer's disease (AD), immunoregulation, and cognition.

In the field of immune regulation, a growing number of studies point to APOE's interaction with many immunological processes, including suppressing T cell proliferation, macrophage functioning regulation, lipid antigen presentation facilitation (by CD1) ^[3] to natural killer T cell as well as modulation of inflammation and oxidation.^[4]

Gene

The gene, ApoE, is mapped to chromosome 19 in a cluster with Apolipoprotein C1 and the Apolipoprotein C2. The APOE gene consists of four exons and three introns, totaling 3597 base pairs. ApoE is transcriptionally activated by the liver X receptor (an important regulator of cholesterol, fatty acid, and glucose homeostasis) and peroxisome proliferator-activated receptor γ, nuclear receptors that form heterodimers with Retinoid X receptors.^[5] In melanocytic cells APOE gene expression may be regulated by MITF.^[6]

Polymorphisms

ApoE is polymorphic,^[7]^[8] with three major isoforms: ApoE2 (cys112, cys158), ApoE3 (cys112, arg158), and ApoE4 (arg112, arg158).^[9] Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158,^[10]^[11]^[12] these differences alter apoE structure and function. These have physiological consequences:

E2 (rs7412) is found in approximately 7 percent of the population.^[13] This variant of the apoprotein binds poorly to cell surface receptors while E3 and E4 bind well.^[14] E2 is associated with both increased and decreased risk for atherosclerosis. Individuals with an E2/E2 combination may clear dietary fat slowly and be at greater risk for early vascular disease and the genetic disorder type III hyperlipoproteinemia—94.4% of such patients are E2/E2, while only ∼2% of E2/E2 develop the disease, so other environmental and genetic factors are likely to be involved (such as cholesterol in the diet and age).^[15]^[16]^[17] E2 has also been implicated in Parkinson's disease.^[18] E2 is no longer associated with Parkinson disease in a larger population association study. ^[19]
E3 (rs429358) is found in approximately 79 percent of the population.^[13] It is considered the "neutral" Apo E genotype.
E4 is found in approximately 14 percent of the population.^[13] E4 has been implicated in atherosclerosis,^[20] Alzheimer's disease,^[21]^[22] impaired cognitive function,^[23]^[24] reduced hippocampal volume,^[24] HIV,^[25] faster disease progression in multiple sclerosis,^[26]^[27] unfavorable outcome after traumatic brain injury,^[28] ischemic cerebrovascular disease,^[29] sleep apnea,^[30]^[31] accelerated telomere shortening ^[32] and reduced neurite outgrowth.^[33]

Alzheimer disease

The E4 variant is the largest known genetic risk factor for late-onset sporadic Alzheimer disease (AD) in a variety of ethnic groups.^[34] Caucasian and Japanese carriers of 2 E4 alleles have between 10 and 30 times the risk of developing AD by 75 years of age, as compared to those not carrying any E4 alleles. While the exact mechanism of how E4 causes such dramatic effects remains to be fully determined, evidence has been presented suggesting an interaction with amyloid.^[35] Alzheimer disease is characterized by build-ups of aggregates of the peptide beta-amyloid. Apolipoprotein E enhances proteolytic break-down of this peptide, both within and between cells. The isoform ApoE-ε4 is not as effective as the others at catalyzing these reactions, resulting in increased vulnerability to AD in individuals with that gene variation.^[36]

The pivotal role of ApoE in AD was first identified through linkage analysis by Margaret Pericak-Vance^[37] while working in the Roses lab at Duke University^[38] Linkage studies were followed by association analysis confirming the role of the ApoE4 allele as a strong genetic risk factor for AD.^[21]^[22]

Although 40-65% of AD patients have at least one copy of the 4 allele, ApoE4 is not a determinant of the disease - at least a third of patients with AD are ApoE4 negative and some ApoE4 homozygotes never develop the disease. Yet those with two e4 alleles have up to 20 times the risk of developing AD.^{[citation needed]} There is also evidence that the ApoE2 allele may serve a protective role in AD.^[39] Thus, the genotype most at risk for Alzheimer disease and at an earlier age is ApoE 4,4. The ApoE 3,4 genotype is at increased risk, though not to the degree that those homozygous for ApoE 4 are. The genotype ApoE 3,3 is considered at normal risk for Alzheimer disease. The genotype ApoE 2,3 is considered at lower risk for Alzheimer disease. Interestingly, people with both a copy of the 2 allele and the 4 allele, ApoE 2,4, are at normal risk, similar to the ApoE 3,3 genotype.

The connection between neuron failure in Alzheimer disease and depleted myelin cholesterol (via ApoE deficiency) has also been described in Cholesterol Depletion and consequently is a known adverse drug reaction to statin therapy.^[40]^[41]^[42]^[43]^[44]

Allele	ε2	ε3	ε4
Estimated worldwide human allele frequencies of ApoE * in Caucasian population^[45]
General Frequency	8.4%	77.9%	13.7%
AD Frequency	3.9%	59.4%	36.7%

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Statin Pathway edit

^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

References

^ "Entrez Gene: APOE apolipoprotein E".
^ Singh PP, Singh M, Mastana SS (2002). "Genetic variation of apolipoproteins in North Indians". Hum. Biol. 74 (5): 673–82. doi:10.1353/hub.2002.0057. PMID 12495081.
^ van den Elzen P, Garg S, León L, Brigl M, Leadbetter EA, Gumperz JE, Dascher CC, Cheng TY, Sacks FM, Illarionov PA, Besra GS, Kent SC, Moody DB, Brenner MB. (2005). "Apolipoprotein-mediated pathways of lipid antigen presentation.". Nature 437 (7060): 906–10. doi:10.1038/nature04001. PMID 16208376.
^ Zhang HL, Wu J, Zhu J (2010). "The Role of Apolipoprotein E in Guillain-Barré Syndrome and Experimental Autoimmune Neuritis". J. Biomed. Biotechnol. 2010: 357412. doi:10.1155/2010/357412. PMC 2825561. PMID 20182542.
^ Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, Liao D, Nagy L, Edwards PA, Curtiss LK, Evans RM, Tontonoz P (2001). "A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis". Mol Cell 7 (1): 161–71. doi:10.1016/S1097-2765(01)00164-2. PMID 11172721.
^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
^ Singh PP, Singh M, Mastana SS (2006). "APOE distribution in world populations with new data from India and the UK". Annals of Human Biology 33 (3): 279–308. doi:10.1080/03014460600594513. PMID 17092867.
^ Eisenberg DTA, Kuzawa CW, Hayes MG. (2010). "Worldwide allele frequencies of the human apoliprotein E (APOE) gene: climate, local adaptations and evolutionary history". American Journal of Physical Anthropology 143 (1): 100–111. doi:10.1002/ajpa.21298. PMID 20734437.
^ Ghebranious N, Ivacic L, Mallum J, and Dokken C (2005). "Detection of ApoE E2, E3 and E4 alleles using MALDI-TOF mass spectrometry and the homogeneous mass-extend technology". Nucleic Acids Res. 33 (17): e149. doi:10.1093/nar/gni155. PMC 1243648. PMID 16204452.
^ http://www.omim.org/entry/107741#0015
^ http://www.omim.org/entry/107741#0001
^ Zuo L, van Dyck CH, Luo X, Kranzler HR, Yang BZ, Gelernter J (2006). "Variation at APOE and STH loci and Alzheimer's disease". Behav Brain Funct 2: 13. doi:10.1186/1744-9081-2-13. PMC 1526745. PMID 16603077.
^ ^a ^b ^c "Alzheimer Research Forum: Meta-Analyses of apolipoprotein E AD Association Studies".
^ Weisgraber KH, Innerarity TL, Mahley RW. (1982). "Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site". J. Biol. Chem. 257 (5): 2518–21. PMID 6277903.
^ Breslow J.L., Zannis V.I., SanGiacomo T.R., Third J.L., Tracy T., Glueck C.J. (1982). "Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2". J. Lipid Res. 23 (8): 1224–1235. PMID 7175379.
^ Feussner G., Feussner V., Hoffmann M.M., Lohrmann J., Wieland H., Marz W. (1998). "Molecular basis of type III hyperlipoproteinemia in Germany". Hum. Mutat. 11 (6): 417–423. doi:10.1002/(SICI)1098-1004(1998)11:6<417::AID-HUMU1>3.0.CO;2-5. PMID 9603433.
^ Civeira F., Pocovi M., Cenarro A., Casao E., Vilella E., Joven J., Gonzalez J., Garcia-Otin A.L., Ordovas J.M. Apo E variants in patients with type III hyperlipoproteinemia. (1996). "Apo E variants in patients with type III hyperlipoproteinemia". Atherosclerosis 127 (2): 273–282. doi:10.1016/S0021-9150(96)05969-2. PMID 9125318.
^ Huang X, Chen PC, Poole C. (2004). "APOE-[epsilon]2 allele associated with higher prevalence of sporadic Parkinson disease". Neurology 62 (12): 2198–202. doi:10.1212/01.wnl.0000130159.28215.6a. PMID 15210882.
^ Federoff M1, Jimenez-Rolando B, Nalls MA, Singleton AB. (2012). "A large study reveals no association between APOE and Parkinson's disease.". Neurobiol Dis. 46 (2): 389–92. doi:10.1016/j.nbd.2012.02.002. PMID 22349451.
^ Mahley RW (April 1988). "Apolipoprotein E: cholesterol transport protein with expanding role in cell biology". Science 240 (4852): 622–30. doi:10.1126/science.3283935. PMID 3283935.
^ ^a ^b Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, 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 (5123): 921–3. doi:10.1126/science.8346443. PMID 8346443.
^ ^a ^b Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, 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 Sciences of the United States of America 90 (5): 1977–1981. doi:10.1073/pnas.90.5.1977. PMC 46003. PMID 8446617.
^ Deary IJ, Whiteman MC, Pattie A, Starr JM, Hayward C, Wright AF, Carothers A, Whalley LJ. (2002). "Cognitive change and the APOE epsilon 4 allele". Nature 418 (6901): 932. doi:10.1038/418932a. PMID 12198535.
^ ^a ^b Farlow MR, He Y, Tekin S, Xu J, Lane R, Charles HC. (2004). "Impact of APOE in mild cognitive impairment.". Neurology 63 (10): 1898–901. doi:10.1212/01.wnl.0000144279.21502.b7. PMID 15557508.
^ Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, Cavrois M, Huang Y, Mahley RW, Dolan MJ, McCune JM, Ahuja SK. (2008). "Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression". Proceedings of the National Academy of Sciences of the United States of America 105 (25): 8718–23. doi:10.1073/pnas.0803526105. PMID 18562290.
^ Chapman J, Vinokurov S, Achiron A, Karussis DM, Mitosek-Szewczyk K, Birnbaum M, Michaelson DM, Korczyn AD (2001). "APOE genotype is a major predictor of long-term progression of disability in MS". Neurology 56 (3): 312–6. doi:10.1212/wnl.56.3.312. PMID 11171894.
^ Schmidt S, Barcellos LF, DeSombre K, Rimmler JB, Lincoln RR, Bucher P, Saunders AM, Lai E, Martin ER, Vance JM, Oksenberg JR, Hauser SL, Pericak-Vance MA, Haines JL; Multiple Sclerosis Genetics Group (2002). "Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis". American Journal of Human Genetics 70 (3): 708–17. doi:10.1086/339269. PMID 11836653.
^ Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, Babaey S, Yehuda B, Groswasser Z (1999). "Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury". Neurology 52 (2): 244–8. doi:10.1212/wnl.52.2.244. PMID 9932938.
^ McCarron MO, Delong D, Alberts MJ. (1999). "APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis". Neurology 53 (6): 1308–11. doi:10.1212/wnl.53.6.1308. PMID 10522889.
^ Kadotani H, Kadotani T, Young T, Peppard PE, Finn L, Colrain IM, Murphy GM Jr, Mignot E (2001). "Association between apolipoprotein E epsilon4 and sleep-disordered breathing in adults". JAMA 285 (22): 2888–90. doi:10.1001/jama.285.22.2888. PMID 11401610.
^ Gottlieb DJ, DeStefano AL, Foley DJ, Mignot E, Redline S, Givelber RJ, Young T. (2004). "APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.". Neurology 63 (4): 664–8. doi:10.1212/01.wnl.0000134671.99649.32. PMID 15326239.
^ Jacobs EG (February 2013). "Accelerated cell aging in female APOE-ε4 carriers: implications for hormone therapy use.". PLOS ONE 8 (2): e54713. doi:10.1371/journal.pone.0054713. PMC 3572118. PMID 23418430.
^ Raber J (May 2008). "AR, apoE, and cognitive function". Horm Behav 53 (5): 706–15. doi:10.1016/j.yhbeh.2008.02.012. PMC 2409114. PMID 18395206.
^ Sadigh-Eteghad S, Talebi M, Farhoudi M (2012). "Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer’s disease, A meta-analysis". Neurosciences (Riyadh) 17 (4): 321–6. PMID 23022896.
^ Wisniewski T, Frangione B (1992). "Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid". Neurosci. Lett. 135 (2): 235–238. doi:10.1016/0304-3940(92)90444-C. PMID 1625800.
^ Jiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE (2008-06-12). "ApoE promotes the proteolytic degradation of Aβ". Neuron (United States: Cell Press) 58 (5): 681–93. doi:10.1016/j.neuron.2008.04.010. PMC 2493297. PMID 18549781. Lay summary – ScienceDaily (2008-06-13).
^ "Margaret Pericak-Vance, Ph.D.". Miami Institute of Human Genomics.
^ Pericak-Vance MA, Bebout JL, Gaskell PC Jr, Yamaoka LH, Hung W-Y, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA, Earl NL, Heyman A, Clark CM, and Roses AD (1991). "Linkage studies in familial Alzheimer disease: Evidence for chromosome 19 linkage". American Journal of Human Genetics 48 (6): 1034–50. PMC 1683100. PMID 2035524.
^ Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC, Rimmler JB, Locke PA, Conneally PM, Schmader KE (1994). "Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease". Nat. Genet. 7 (2): 180–4. doi:10.1038/ng0694-180. PMID 7920638.
^ Mason RP, Shoemaker WJ, Shajenko L, Chambers TE, Herbette LG (1992). "Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol". Neurobiol. Aging 13 (3): 413–9. doi:10.1016/0197-4580(92)90116-F. PMID 1625771.
^ Eckert GP, Kirsch C, Leutz S, Wood WG, Müller WE (September 2003). "Cholesterol modulates amyloid beta-peptide's membrane interactions". Pharmacopsychiatry. 36 Suppl 2: S136–43. doi:10.1055/s-2003-43059. PMID 14574628.
^ Howland DS, Trusko SP, Savage MJ, Reaume AG, Lang DM, Hirsch JD, Maeda N, Siman R, Greenberg BD, Scott RW, Flood DG (June 1998). "Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol". J. Biol. Chem. 273 (26): 16576–82. doi:10.1074/jbc.273.26.16576. PMID 9632729.
^ Lepara O, Valjevac A, Alajbegović A, Zaćiragić A, Nakas-Ićindić E (August 2009). "Decreased serum lipids in patients with probable Alzheimer's disease". Bosn J Basic Med Sci 9 (3): 215–20. PMID 19754476.
^ Golomb BA, Evans MA (2008). "Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism". Am J Cardiovasc Drugs 8 (6): 373–418. doi:10.2165/0129784-200808060-00004. PMC 2849981. PMID 19159124.
^ Farrer L.A., Cupples L.A., Haines J.L., Hyman B., Kukull W.A., Mayeux R., Myers R.H., Pericak-Vance M.A., Risch N., van Duijn C.N. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. (1997). JAMA 278: 1349–1356. doi:10.1001/jama.1997.03550160069041. PMID 9343467.

External links

Apolipoproteins E at the US National Library of Medicine Medical Subject Headings (MeSH)
apoe4.info - website for APOE-epsilon-4 carriers

UpToDate Contents

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1. アルツハイマー病の遺伝学 genetics of alzheimer disease
2. リポ蛋白の分類、代謝、およびアテローム性動脈硬化症における役割 lipoprotein classification metabolism and role in atherosclerosis
3. LDLコレステロール代謝の遺伝性疾患 inherited disorders of ldl cholesterol metabolism
4. 成人における早期発症の認知症 early onset dementia in adults
5. 脳アミロイドアンギオパチー cerebral amyloid angiopathy

English Journal

ApoE isoform modulates effects of cranial (56)Fe irradiation on spatial learning and memory in the water maze.

Yeiser LA, Villasana LE, Raber J.SourceDepartment of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, United States.
Behavioural brain research.Behav Brain Res.2013 Jan 15;237:207-14. doi: 10.1016/j.bbr.2012.09.029. Epub 2012 Sep 24.
Apolipoprotein E, which plays an important role in lipid transport and metabolism and neuronal repair, might modulate the CNS risk following (56)Fe irradiation exposure during space missions. In this study, we investigated this risk by behavioral and cognitive testing male E2, E3, and E4 mice 3 mont
PMID 23018124

Contrast enhancement by lipid-based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study.

den Adel B, van der Graaf LM, Que I, Strijkers GJ, Löwik CW, Poelmann RE, van der Weerd L.SourceDepartment of Anatomy and Embryology, Leiden University Medical Center, Leiden, the Netherlands.
Contrast media & molecular imaging.Contrast Media Mol Imaging.2013 Jan;8(1):63-71. doi: 10.1002/cmmi.1496.
The use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium-based contrast agents to enhance atherosclerotic plaques in ApoE(-/-) mice was evaluated with MRI. We obtain
PMID 23109394

Japanese Journal

Deletion of sphingosine-1-phosphate receptor-2 inhibits proinflammatory activities of macrophages and atherosclerosis in apoE-deficient mice

WANG Fei,OKAMOTO Yasuo,INOKI Isao,YOSHIOKA Kazuaki,TAKUWA Noriko,OHKAWA Ryunosuke,YATOMI Yutaka,KINOSHITA Makoto,TAKUWA Yoh
脂質生化学研究 53, 227-230, 2011-04-28
NAID 10028179025

apoE-KOマウス大動脈の動脈硬化巣形成前から進行する脂質過酸化物の蓄積に関与する因子の探索

加藤里奈,林暢孝,宮越由佳,天日雅行,鶴巻実香,鈴木裕之,松井浩志,相内敏弘,小浜孝士,山口智広,板部洋之
脂質生化学研究 53, 224-226, 2011-04-28
NAID 10028179023

「異常βリポ蛋白血症」

Apolipoprotein E
	; PDB rendering based on 1b68.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1B68, 1BZ4, 1EA8, 1GS9, 1H7I, 1LE2, 1LE4, 1LPE, 1NFN, 1NFO, 1OEF, 1OEG, 1OR2, 1OR3, 2KC3, 2KNY, 2L7B
Identifiers
Symbols	APOE ; AD2; LDLCQ5; LPG
External IDs	OMIM: 107741 MGI: 88057 HomoloGene: 30951 GeneCards: APOE Gene
Gene ontology
Molecular function	• beta-amyloid binding; • lipid transporter activity; • protein binding; • phospholipid binding; • heparin binding; • lipid binding; • antioxidant activity; • cholesterol transporter activity; • identical protein binding; • protein homodimerization activity; • hydroxyapatite binding; • metal chelating activity; • protein heterodimerization activity; • tau protein binding; • low-density lipoprotein particle receptor binding; • phosphatidylcholine-sterol O-acyltransferase activator activity; • very-low-density lipoprotein particle receptor binding; • lipoprotein particle binding;
Cellular component	• extracellular region; • extracellular space; • cytoplasm; • early endosome; • late endosome; • Golgi apparatus; • plasma membrane; • dendrite; • extrinsic to external side of plasma membrane; • very-low-density lipoprotein particle; • low-density lipoprotein particle; • intermediate-density lipoprotein particle; • high-density lipoprotein particle; • chylomicron; • neuronal cell body;
Biological process	• response to reactive oxygen species; • retinoid metabolic process; • negative regulation of endothelial cell proliferation; • response to dietary excess; • lipid metabolic process; • triglyceride metabolic process; • cholesterol catabolic process; • cellular calcium ion homeostasis; • receptor-mediated endocytosis; • induction of apoptosis; • cytoskeleton organization; • G-protein coupled receptor signaling pathway; • nitric oxide mediated signal transduction; • synaptic transmission, cholinergic; • aging; • phototransduction, visible light; • cholesterol metabolic process; • cell death; • regulation of gene expression; • negative regulation of platelet activation; • positive regulation of cholesterol esterification; • positive regulation of cholesterol efflux; • peripheral nervous system axon regeneration; • cGMP-mediated signaling; • negative regulation of blood coagulation; • regulation of axon extension; • positive regulation of cGMP biosynthetic process; • regulation of Cdc42 protein signal transduction; • response to retinoic acid; • positive regulation of low-density lipoprotein particle receptor catabolic process; • response to insulin stimulus; • cholesterol efflux; • phospholipid efflux; • very-low-density lipoprotein particle remodeling; • low-density lipoprotein particle remodeling; • high-density lipoprotein particle remodeling; • high-density lipoprotein particle assembly; • chylomicron remnant clearance; • high-density lipoprotein particle clearance; • very-low-density lipoprotein particle clearance; • lipoprotein metabolic process; • lipoprotein biosynthetic process; • lipoprotein catabolic process; • vasodilation; • cholesterol homeostasis; • negative regulation of apoptotic process; • negative regulation of MAP kinase activity; • negative regulation of neuron apoptotic process; • negative regulation of blood vessel endothelial cell migration; • reverse cholesterol transport; • small molecule metabolic process; • response to ethanol; • negative regulation of cholesterol biosynthetic process; • positive regulation of axon extension; • intracellular transport; • regulation of neuronal synaptic plasticity; • oligodendrocyte differentiation; • artery morphogenesis; • negative regulation of inflammatory response; • positive regulation of nitric-oxide synthase activity; • positive regulation of membrane protein ectodomain proteolysis; • maintenance of location in cell; • cellular response to interleukin-1; • cellular response to growth factor stimulus; • cellular response to cholesterol;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

　　[★]

英: dysbetalipoproteinemia
同: 高リポ蛋白血症III型 hyperlipoproteinemia type III, ブロードβ病 broad-β disease
関: III型高脂血症、apoE、リポ蛋白

概念

病因

アポ蛋白E遺伝子異常

familial type III hyperlipidemia: 機能正常なアポリポ蛋白E(apoE)を欠く
カイロミクロンレムナントが蓄積する。

疫学

病変形成＆病理

症状

xanthoma
アキレス腱炎はない (⇔IIa型高脂血症)

診断

検査

治療

予後

予防

「アポE」

　　[★]

英: apoE、apolipoprotein E
関: アポリポ蛋白E、アポリポタンパクE、アポリポタンパク質E、アポリポ蛋白質E

「アポリポ蛋白E」

　　[★]

英: apolipoprotein E、apoE、apo E
関: アポE、アポリポタンパクE、アポリポタンパク質E、アポリポ蛋白質E

「アポリポ蛋白質E」

　　[★]

英: apolipoprotein E, apo E, apoE
同: アポE
関: 脂質異常症

「apoE receptor」

　　[★]

アポリポタンパク質E受容体、アポリポタンパク質Eレセプター、アポリポ蛋白E受容体、アポリポ蛋白Eレセプター、アポE受容体、アポEレセプター、apoE受容体、apoEレセプター

関: alpha 2-macroglobulin receptor、apolipoprotein E receptor、LDL-receptor related protein 1

「apoE受容体」

　　[★]

英: apoE receptor
関: アポリポ蛋白E受容体、アポリポ蛋白Eレセプター、アポE受容体、アポEレセプター、apoEレセプター、アポリポタンパク質Eレセプター、アポリポタンパク質E受容体

「apoEレセプター」

　　[★]

英: apoE receptor
関: アポリポ蛋白E受容体、アポリポ蛋白Eレセプター、apoE受容体、アポE受容体、アポEレセプター、アポリポタンパク質Eレセプター、アポリポタンパク質E受容体

「apoE4」

　　[★]

ア・リ・タンパク質E4、ア・リ・蛋白E4、ア・E4

関: apolipoprotein E4

「apo」

　　[★]

アポリポタンパク質、アポリポ蛋白質、アポリポタンパク、アポリポ蛋白、アポ

関: apolipoprotein

[WikiPathways-46] The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

[entrez-1] "Entrez Gene: APOE apolipoprotein E".

[2] Singh PP, Singh M, Mastana SS (2002). "Genetic variation of apolipoproteins in North Indians". Hum. Biol. 74 (5): 673–82. doi:10.1353/hub.2002.0057. PMID 12495081.

[3] van den Elzen P, Garg S, León L, Brigl M, Leadbetter EA, Gumperz JE, Dascher CC, Cheng TY, Sacks FM, Illarionov PA, Besra GS, Kent SC, Moody DB, Brenner MB. (2005). "Apolipoprotein-mediated pathways of lipid antigen presentation.". Nature 437 (7060): 906–10. doi:10.1038/nature04001. PMID 16208376.

[pmid20182542-4] Zhang HL, Wu J, Zhu J (2010). "The Role of Apolipoprotein E in Guillain-Barré Syndrome and Experimental Autoimmune Neuritis". J. Biomed. Biotechnol. 2010: 357412. doi:10.1155/2010/357412. PMC 2825561. PMID 20182542.

[pmid11172721-5] Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, Liao D, Nagy L, Edwards PA, Curtiss LK, Evans RM, Tontonoz P (2001). "A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis". Mol Cell 7 (1): 161–71. doi:10.1016/S1097-2765(01)00164-2. PMID 11172721.

[pmid19067971-6] Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[pmid17092867-7] Singh PP, Singh M, Mastana SS (2006). "APOE distribution in world populations with new data from India and the UK". Annals of Human Biology 33 (3): 279–308. doi:10.1080/03014460600594513. PMID 17092867.

[10.1002.2Fajpa.21298-8] Eisenberg DTA, Kuzawa CW, Hayes MG. (2010). "Worldwide allele frequencies of the human apoliprotein E (APOE) gene: climate, local adaptations and evolutionary history". American Journal of Physical Anthropology 143 (1): 100–111. doi:10.1002/ajpa.21298. PMID 20734437.

[9] Ghebranious N, Ivacic L, Mallum J, and Dokken C (2005). "Detection of ApoE E2, E3 and E4 alleles using MALDI-TOF mass spectrometry and the homogeneous mass-extend technology". Nucleic Acids Res. 33 (17): e149. doi:10.1093/nar/gni155. PMC 1243648. PMID 16204452.

[10] ttp://www.omim.org/entry/107741#0015

[11] ttp://www.omim.org/entry/107741#0001

[pmid16603077-12] Zuo L, van Dyck CH, Luo X, Kranzler HR, Yang BZ, Gelernter J (2006). "Variation at APOE and STH loci and Alzheimer's disease". Behav Brain Funct 2: 13. doi:10.1186/1744-9081-2-13. PMC 1526745. PMID 16603077.

[Meta-analysis-13] "Alzheimer Research Forum: Meta-Analyses of apolipoprotein E AD Association Studies".

[14] Weisgraber KH, Innerarity TL, Mahley RW. (1982). "Abnormal lipoprotein receptor-binding activity of the human E apoprotein due to cysteine-arginine interchange at a single site". J. Biol. Chem. 257 (5): 2518–21. PMID 6277903.

[15] Breslow J.L., Zannis V.I., SanGiacomo T.R., Third J.L., Tracy T., Glueck C.J. (1982). "Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2". J. Lipid Res. 23 (8): 1224–1235. PMID 7175379.

[16] Feussner G., Feussner V., Hoffmann M.M., Lohrmann J., Wieland H., Marz W. (1998). "Molecular basis of type III hyperlipoproteinemia in Germany". Hum. Mutat. 11 (6): 417–423. doi:10.1002/(SICI)1098-1004(1998)11:6<417::AID-HUMU1>3.0.CO;2-5. PMID 9603433.

[17] Civeira F., Pocovi M., Cenarro A., Casao E., Vilella E., Joven J., Gonzalez J., Garcia-Otin A.L., Ordovas J.M. Apo E variants in patients with type III hyperlipoproteinemia. (1996). "Apo E variants in patients with type III hyperlipoproteinemia". Atherosclerosis 127 (2): 273–282. doi:10.1016/S0021-9150(96)05969-2. PMID 9125318.

[18] Huang X, Chen PC, Poole C. (2004). "APOE-[epsilon]2 allele associated with higher prevalence of sporadic Parkinson disease". Neurology 62 (12): 2198–202. doi:10.1212/01.wnl.0000130159.28215.6a. PMID 15210882.

[19] Federoff M1, Jimenez-Rolando B, Nalls MA, Singleton AB. (2012). "A large study reveals no association between APOE and Parkinson's disease.". Neurobiol Dis. 46 (2): 389–92. doi:10.1016/j.nbd.2012.02.002. PMID 22349451.

[pmid3283935-20] Mahley RW (April 1988). "Apolipoprotein E: cholesterol transport protein with expanding role in cell biology". Science 240 (4852): 622–30. doi:10.1126/science.3283935. PMID 3283935.

[pmid8346443-21] Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, 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 (5123): 921–3. doi:10.1126/science.8346443. PMID 8346443.

[pmid8446617-22] Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, 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 Sciences of the United States of America 90 (5): 1977–1981. doi:10.1073/pnas.90.5.1977. PMC 46003. PMID 8446617.

[23] Deary IJ, Whiteman MC, Pattie A, Starr JM, Hayward C, Wright AF, Carothers A, Whalley LJ. (2002). "Cognitive change and the APOE epsilon 4 allele". Nature 418 (6901): 932. doi:10.1038/418932a. PMID 12198535.

[Cognitive_Impairment-24] Farlow MR, He Y, Tekin S, Xu J, Lane R, Charles HC. (2004). "Impact of APOE in mild cognitive impairment.". Neurology 63 (10): 1898–901. doi:10.1212/01.wnl.0000144279.21502.b7. PMID 15557508.

[25] Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, Cavrois M, Huang Y, Mahley RW, Dolan MJ, McCune JM, Ahuja SK. (2008). "Apolipoprotein (apo) E4 enhances HIV-1 cell entry in vitro, and the APOE epsilon4/epsilon4 genotype accelerates HIV disease progression". Proceedings of the National Academy of Sciences of the United States of America 105 (25): 8718–23. doi:10.1073/pnas.0803526105. PMID 18562290.

[26] Chapman J, Vinokurov S, Achiron A, Karussis DM, Mitosek-Szewczyk K, Birnbaum M, Michaelson DM, Korczyn AD (2001). "APOE genotype is a major predictor of long-term progression of disability in MS". Neurology 56 (3): 312–6. doi:10.1212/wnl.56.3.312. PMID 11171894.

[27] Schmidt S, Barcellos LF, DeSombre K, Rimmler JB, Lincoln RR, Bucher P, Saunders AM, Lai E, Martin ER, Vance JM, Oksenberg JR, Hauser SL, Pericak-Vance MA, Haines JL; Multiple Sclerosis Genetics Group (2002). "Association of polymorphisms in the apolipoprotein E region with susceptibility to and progression of multiple sclerosis". American Journal of Human Genetics 70 (3): 708–17. doi:10.1086/339269. PMID 11836653.

[28] Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, Babaey S, Yehuda B, Groswasser Z (1999). "Apolipoprotein E-epsilon4 genotype predicts a poor outcome in survivors of traumatic brain injury". Neurology 52 (2): 244–8. doi:10.1212/wnl.52.2.244. PMID 9932938.

[29] McCarron MO, Delong D, Alberts MJ. (1999). "APOE genotype as a risk factor for ischemic cerebrovascular disease: a meta-analysis". Neurology 53 (6): 1308–11. doi:10.1212/wnl.53.6.1308. PMID 10522889.

[30] Kadotani H, Kadotani T, Young T, Peppard PE, Finn L, Colrain IM, Murphy GM Jr, Mignot E (2001). "Association between apolipoprotein E epsilon4 and sleep-disordered breathing in adults". JAMA 285 (22): 2888–90. doi:10.1001/jama.285.22.2888. PMID 11401610.

[31] Gottlieb DJ, DeStefano AL, Foley DJ, Mignot E, Redline S, Givelber RJ, Young T. (2004). "APOE epsilon4 is associated with obstructive sleep apnea/hypopnea: the Sleep Heart Health Study.". Neurology 63 (4): 664–8. doi:10.1212/01.wnl.0000134671.99649.32. PMID 15326239.

[pmid23418430-32] Jacobs EG (February 2013). "Accelerated cell aging in female APOE-ε4 carriers: implications for hormone therapy use.". PLOS ONE 8 (2): e54713. doi:10.1371/journal.pone.0054713. PMC 3572118. PMID 23418430.

[pmid18395206-33] Raber J (May 2008). "AR, apoE, and cognitive function". Horm Behav 53 (5): 706–15. doi:10.1016/j.yhbeh.2008.02.012. PMC 2409114. PMID 18395206.

[34] Sadigh-Eteghad S, Talebi M, Farhoudi M (2012). "Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer’s disease, A meta-analysis". Neurosciences (Riyadh) 17 (4): 321–6. PMID 23022896.

[pmid1625800-35] Wisniewski T, Frangione B (1992). "Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid". Neurosci. Lett. 135 (2): 235–238. doi:10.1016/0304-3940(92)90444-C. PMID 1625800.

[Neuron-36] Jiang Q, Lee CY, Mandrekar S, Wilkinson B, Cramer P, Zelcer N, Mann K, Lamb B, Willson TM, Collins JL, Richardson JC, Smith JD, Comery TA, Riddell D, Holtzman DM, Tontonoz P, Landreth GE (2008-06-12). "ApoE promotes the proteolytic degradation of Aβ". Neuron (United States: Cell Press) 58 (5): 681–93. doi:10.1016/j.neuron.2008.04.010. PMC 2493297. PMID 18549781. Lay summary – ScienceDaily (2008-06-13).

[urlMiami_Institute_of_Human_Genomics_-_People-37] "Margaret Pericak-Vance, Ph.D.". Miami Institute of Human Genomics.

[pmid_2035524-38] Pericak-Vance MA, Bebout JL, Gaskell PC Jr, Yamaoka LH, Hung W-Y, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA, Earl NL, Heyman A, Clark CM, and Roses AD (1991). "Linkage studies in familial Alzheimer disease: Evidence for chromosome 19 linkage". American Journal of Human Genetics 48 (6): 1034–50. PMC 1683100. PMID 2035524.

[pmid7920638-39] Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC, Rimmler JB, Locke PA, Conneally PM, Schmader KE (1994). "Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease". Nat. Genet. 7 (2): 180–4. doi:10.1038/ng0694-180. PMID 7920638.

[pmid1625771-40] Mason RP, Shoemaker WJ, Shajenko L, Chambers TE, Herbette LG (1992). "Evidence for changes in the Alzheimer's disease brain cortical membrane structure mediated by cholesterol". Neurobiol. Aging 13 (3): 413–9. doi:10.1016/0197-4580(92)90116-F. PMID 1625771.

[pmid14574628-41] Eckert GP, Kirsch C, Leutz S, Wood WG, Müller WE (September 2003). "Cholesterol modulates amyloid beta-peptide's membrane interactions". Pharmacopsychiatry. 36 Suppl 2: S136–43. doi:10.1055/s-2003-43059. PMID 14574628.

[pmid9632729-42] Howland DS, Trusko SP, Savage MJ, Reaume AG, Lang DM, Hirsch JD, Maeda N, Siman R, Greenberg BD, Scott RW, Flood DG (June 1998). "Modulation of secreted beta-amyloid precursor protein and amyloid beta-peptide in brain by cholesterol". J. Biol. Chem. 273 (26): 16576–82. doi:10.1074/jbc.273.26.16576. PMID 9632729.

[pmid19754476-43] Lepara O, Valjevac A, Alajbegović A, Zaćiragić A, Nakas-Ićindić E (August 2009). "Decreased serum lipids in patients with probable Alzheimer's disease". Bosn J Basic Med Sci 9 (3): 215–20. PMID 19754476.

[pmid19159124-44] Golomb BA, Evans MA (2008). "Statin Adverse Effects: A Review of the Literature and Evidence for a Mitochondrial Mechanism". Am J Cardiovasc Drugs 8 (6): 373–418. doi:10.2165/0129784-200808060-00004. PMC 2849981. PMID 19159124.

[45] Farrer L.A., Cupples L.A., Haines J.L., Hyman B., Kukull W.A., Mayeux R., Myers R.H., Pericak-Vance M.A., Risch N., van Duijn C.N. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. (1997). JAMA 278: 1349–1356. doi:10.1001/jama.1997.03550160069041. PMID 9343467.

リンク元	「異常βリポ蛋白血症」「アポE」「アポリポ蛋白E」「アポリポ蛋白質E」
拡張検索	「apoE receptor」「apoE受容体」「apoEレセプター」「apoE4」
関連記事	「apo」

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apoE