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the 5th letter of the Roman alphabet (同)e
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/02 07:51:43」(JST)

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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.^[2] This protein is involved in Alzheimer’s disease and cardiovascular disease.^[3]

Structure

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.^[4] In melanocytic cells APOE gene expression may be regulated by MITF.^[5]

Protein

APOE is 299 amino acids long and contains multiple amphipathic α-helices. According to crystallography studies, a hinge region connects the N- and C-terminal regions of the protein. The N-terminal region (residues 1–167) forms an anti-parallel four-helix bundle such that the non-polar sides face inside the protein. Meanwhile, the C-terminal domain (residues 206-299) contains three α-helices which form a large exposed hydrophobic surface and interact with those in the N-terminal helix bundle domain through hydrogen bonds and salt-bridges. The C-terminal region also contains a low density lipoprotein receptor (LDLR)-binding site.^[6]

Polymorphisms

APOE is polymorphic,^[7]^[8] with three major alleles: ApoE2 (cys112, cys158), ApoE3 (cys112, arg158), and ApoE4 (arg112, arg158).^[3]^[9]^[10] Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158,^[11]^[12]^[13] these differences alter APOE structure and function. These have physiological consequences:

E2 (rs7412) has an allele frequency of approximately 7 percent.^[14] This variant of the apoprotein binds poorly to cell surface receptors while E3 and E4 bind well.^[15] 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).^[16]^[17]^[18] E2 has also been implicated in Parkinson's disease,^[19] but this finding was not replicated in a larger population association study.^[20]
E3 (rs429358) has an allele frequency of approximately 79 percent.^[14] It is considered the "neutral" Apo E genotype.
E4 has an allele frequency of approximately 14 percent.^[14] E4 has been implicated in atherosclerosis,^[21] Alzheimer's disease,^[22]^[23] impaired cognitive function,^[24]^[25] reduced hippocampal volume,^[25] HIV,^[26] faster disease progression in multiple sclerosis,^[27]^[28] unfavorable outcome after traumatic brain injury,^[29] ischemic cerebrovascular disease,^[30] sleep apnea,^[31]^[32] accelerated telomere shortening ^[33] and reduced neurite outgrowth.^[34] A notable advantage of the E4 allele (relative to E2 and E3) is a positive association with higher levels of vitamin D, which may help explain its prevalence despite its seeming complicity in various diseases or disorders.^[35]

However, there is much to be learned about these APOE isoforms, including the interaction of other potentially protective genetic polymorphisms, so caution is advised before making determinant statements about the influence of APOE polymorphisms; this is particularly true as it relates to how APOE isoforms influence cognition and the development of Alzheimer’s Disease. In addition, there is no evidence that APOE polymorphisms influence cognition in younger age groups (other than possible increased episodic memory ability and neural efficiency in younger APOE4 age groups), nor is there evidence that the APOE4 isoform places individuals at increased risk for any infectious disease.^[36]

Function

APOE 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.^[9] 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.^[37] There are seven currently identified mammalian receptors for APOE which belong to the evolutionarily conserved LDLR family.^[38]

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.^[1] 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.^[3] Though the exact mechanisms remain to be elucidated, isoform 4 of APOE, encoded by an APOE allele, has been associated with increased calcium ion levels and apoptosis following mechanical injury.^[39]

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) ^[40] to natural killer T cell as well as modulation of inflammation and oxidation.^[41] APOE is produced by macrophages and APOE secretion has been shown to be restricted to classical monocytes in PBMC, and the secretion of APOE by monocytes is down regulated by inflammatory cytokines and upregulated by TGF-beta.^[42]

Clinical Significance

Alzheimer's disease

The E4 variant is the largest known genetic risk factor for late-onset sporadic Alzheimer's disease (AD) in a variety of ethnic groups.^[43] 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.^[44] Alzheimer's 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 promoting these reactions, resulting in increased vulnerability to AD in individuals with that gene variation.^[45]

The pivotal role of ApoE in AD was first identified through linkage analysis by Margaret Pericak-Vance^[46] while working in the Roses lab at Duke University^[47] Linkage studies were followed by association analysis confirming the role of the ApoE4 allele as a strong genetic risk factor for AD.^[22]^[23]

Although 40-65% of AD patients have at least one copy of the ε4 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 ε4 alleles have up to 20 times the risk of developing AD.^[48] There is also evidence that the ApoE2 allele may serve a protective role in AD.^[49] Thus, the genotype most at risk for Alzheimer's disease and at an earlier age is ApoE 4,4. Using genotype ApoE 3,3 as a benchmark (with the persons who have this genotype regarded as having a risk level of 1.0), individuals with genotype ApoE4,4 have an odds ratio of 14.9 of developing Alzheimer's disease. Individuals with the ApoE 3,4 genotype face an odds ratio of 3.2, and people with a copy of the 2 allele and the 4 allele (ApoE2,4), have an odds ratio of 2.6. Persons with one copy each of the 2 allele and the 3 allele (ApoE2,3) have an odds ratio of 0.6. Persons with two copies of the 2 allele (ApoE2,2) also have an odds ratio of 0.6.^[50]

Allele	ε2	ε3	ε4
Estimated worldwide human allele frequencies of ApoE * in Caucasian population^[50]
General Frequency	8.4%	77.9%	13.7%
AD Frequency	3.9%	59.4%	36.7%

Atherosclerosis

Knockout mice that lack the apolipoprotein-E gene (ApoE⁻/⁻) develop extreme hypercholesterolemia when fed a high-fat diet.^[51]

Interactions

Interactive pathway map

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

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|{{{bSize}}}px|alt=Statin Pathway edit]]

File:StatinPathway_WP430.png

Statin Pathway edit

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

References

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^ ^a ^b ^c (ed.), Ian P. Stolerman (2010). Encyclopedia of psychopharmacology (Online-Ausg. ed.). Berlin: Springer. ISBN 9783540686989.
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^ Online 'Mendelian Inheritance in Man' (OMIM) APOE3 isoform, hyperlipoproteinemia, type III, autosomal recessive -107741#0015
^ Online 'Mendelian Inheritance in Man' (OMIM) APOE3 isoform, APOE, CYS112 and ARG158 -107741#0001
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^ Chapman J, Vinokurov S, Achiron A, Karussis DM, Mitosek-Szewczyk K, Birnbaum M, Michaelson DM, Korczyn AD (Feb 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 (Mar 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 (Jan 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 (Oct 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, Mignot E (Jun 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 (Aug 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.
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^ Zhang HL, Wu J, Zhu J (2010). "The role of apolipoprotein E in Guillain-Barré syndrome and experimental autoimmune neuritis". Journal of Biomedicine & Biotechnology 2010: 357412. doi:10.1155/2010/357412. PMC 2825561. PMID 20182542.
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^ 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 (Jun 2008). "ApoE promotes the proteolytic degradation of Abeta". Neuron (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, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA (Jun 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.
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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

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

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. 脳アミロイドアンギオパチー cerebral amyloid angiopathy
5. 心血管疾患と同等のリスクと確立した危険因子の概要 overview of the risk equivalents and established risk factors for cardiovascular disease

English Journal

Plasma apolipoprotein E and severity of suicidal behaviour.

Asellus P1, Nordström P2, Nordström AL2, Jokinen J3.
Journal of affective disorders.J Affect Disord.2016 Jan 15;190:137-42. doi: 10.1016/j.jad.2015.09.024. Epub 2015 Oct 22.
There is evidence for association between low cholesterol levels and suicidal behaviour. Since apolipoprotein E (ApoE) is involved in the cholesterol metabolism in both the periphery and in the central nervous system; it may be of particular interest in the neurobiology of suicidal behaviour. Furthe
PMID 26519632

Apolipoprotein E Isoforms and AMD.

Toops KA1, Tan LX2, Lakkaraju A3,4,5.
Advances in experimental medicine and biology.Adv Exp Med Biol.2016;854:3-9. doi: 10.1007/978-3-319-17121-0_1.
The cholesterol transporting protein apolipoprotein E (ApoE) occurs in three allelic variants in humans unlike in other species. The resulting protein isoforms E2, E3 and E4 exhibit differences in lipid binding, integrating into lipoprotein particles and affinity for lipoprotein receptors. ApoE isof
PMID 26427386

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia: A Population-Based Study.

Wolters FJ1, de Bruijn RF1, Hofman A1, Koudstaal PJ1, Ikram MA2; Heart Brain Connection Collaborative Research Group.
Arteriosclerosis, thrombosis, and vascular biology.Arterioscler Thromb Vasc Biol.2016 Jan;36(1):204-10. doi: 10.1161/ATVBAHA.115.306768. Epub 2015 Nov 19.
OBJECTIVE: Cerebral vasoreactivity (CVR) is a key factor in maintenance of continuous cerebral perfusion and a marker of (micro)vascular damage. We aimed to determine the longitudinal relation between CVR and the risk of dementia in the general population.APPROACH AND RESULTS: We determined CVR in n
PMID 26586657

Japanese Journal

Statins Induce the Gene Expression of Apolipoprotein A5 in HepG2 Cells

Arishima Hiroaki,Matsunaga Akira,Uehara Yoshinari,Niimura Hideya,Zhang Bo,Ohwaki Kazuo,Hayashida Kazue,Yoshimizu Kayo,Saku Keijiro
福岡大学医学紀要 38(4), 161-169, 2011-12
NAID 110008720006

Apolipoprotein E遺伝子 (認知症学(上)その解明と治療の最新知見) -- (基礎編認知症関連分子生物学)

桑野良三,宮下哲典
日本臨床 69(-) (1008), 93-97, 2011-10
NAID 40019021402

「アポE」

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; APO-E; 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; • cholesterol binding; • antioxidant activity; • cholesterol transporter activity; • identical protein binding; • protein homodimerization activity; • metal chelating 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; • nucleus; • cytoplasm; • early endosome; • endoplasmic reticulum; • Golgi apparatus; • plasma membrane; • membrane; • dendrite; • extracellular matrix; • very-low-density lipoprotein particle; • low-density lipoprotein particle; • intermediate-density lipoprotein particle; • high-density lipoprotein particle; • chylomicron; • neuronal cell body; • extracellular exosome; • endocytic vesicle lumen; • blood microparticle; • extracellular vesicle;
Biological process	• response to reactive oxygen species; • retinoid metabolic process; • negative regulation of endothelial cell proliferation; • response to dietary excess; • triglyceride metabolic process; • cholesterol biosynthetic process; • cholesterol catabolic process; • cellular calcium ion homeostasis; • receptor-mediated endocytosis; • cytoskeleton organization; • G-protein coupled receptor signaling pathway; • nitric oxide mediated signal transduction; • synaptic transmission, cholinergic; • phototransduction, visible light; • cholesterol metabolic process; • regulation of gene expression; • negative regulation of platelet activation; • positive regulation of cholesterol esterification; • positive regulation of cholesterol efflux; • long-chain fatty acid transport; • protein import; • virion assembly; • triglyceride catabolic process; • cGMP-mediated signaling; • negative regulation of blood coagulation; • regulation of axon extension; • positive regulation of cGMP biosynthetic process; • neuron projection regeneration; • regulation of Cdc42 protein signal transduction; • positive regulation of low-density lipoprotein particle receptor catabolic process; • 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 MAP kinase activity; • negative regulation of neuron apoptotic process; • negative regulation of blood vessel endothelial cell migration; • reverse cholesterol transport; • small molecule metabolic process; • positive regulation by host of viral process; • negative regulation of cholesterol biosynthetic process; • positive regulation of lipid biosynthetic process; • intracellular transport; • regulation of neuronal synaptic plasticity; • artery morphogenesis; • negative regulation of inflammatory response; • positive regulation of nitric-oxide synthase activity; • positive regulation of membrane protein ectodomain proteolysis; • negative regulation of lipid biosynthetic process; • maintenance of location in cell; • fatty acid homeostasis; • positive regulation of dendritic spine development; • negative regulation of dendritic spine development; • negative regulation of cholesterol efflux; • alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor clustering; • N-methyl-D-aspartate receptor clustering; • regulation of beta-amyloid clearance; • regulation of neuron death; • negative regulation of neuron death; • positive regulation of neuron death; • negative regulation of postsynaptic membrane organization; • positive regulation of postsynaptic membrane organization; • negative regulation of presynaptic membrane organization; • positive regulation of presynaptic membrane organization; • positive regulation of beta-amyloid formation; • negative regulation of beta-amyloid formation; • regulation of tau-protein kinase activity; • negative regulation of dendritic spine maintenance; • positive regulation of dendritic spine maintenance; • positive regulation of phospholipid efflux; • positive regulation of neurofibrillary tangle assembly; • negative regulation of phospholipid efflux; • negative regulation of lipid transport across blood brain barrier; • positive regulation of lipid transport across blood brain barrier;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; 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

「アポリポタンパクE」

　　[★]

英: apolipoprotein E
関: アポE、アポリポ蛋白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

「apolipoprotein E 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

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

「apolipoprotein E2」

　　[★]

ア・リ・タンパク質E2

関: apo E2、apoE2

「apolipoprotein E4」

　　[★]

ア・リ・タンパク質E4

関: apoE4

「apolipoprotein E3」

　　[★]

ア・リ・タンパク質E3

「apolipoprotein」

　　[★]

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、アポリポプロテイン

関: apo

「Es」

　　[★] アインスタイニウム

関: einsteinium

「apolipoproteins」

　　[★]

同: apolipoprotein

同: apolipoprotein

「E」

　　[★]

[WikiPathways-52] The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

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

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[encyclopedia-3] (ed.), Ian P. Stolerman (2010). Encyclopedia of psychopharmacology (Online-Ausg. ed.). Berlin: Springer. ISBN 9783540686989.

[pmid11172721-4] Chawla A, Boisvert WA, Lee CH, Laffitte BA, Barak Y, Joseph SB, Liao D, Nagy L, Edwards PA, Curtiss LK, Evans RM, Tontonoz P (Jan 2001). "A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis". Molecular Cell 7 (1): 161–71. doi:10.1016/S1097-2765(01)00164-2. PMID 11172721.

[pmid19067971-5] Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[pmid25328986-6] Phillips MC (Sep 2014). "Apolipoprotein E isoforms and lipoprotein metabolism". IUBMB Life 66 (9): 616–23. doi:10.1002/iub.1314. PMID 25328986.

[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 DT, Kuzawa CW, Hayes MG (Sep 2010). "Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history". American Journal of Physical Anthropology 143 (1): 100–11. doi:10.1002/ajpa.21298. PMID 20734437.

[cardiogenetics-9] Baars HF, van der Smagt JJ, Doevandans PA (2011). Clinical Cardiogenetics. London: Springer. ISBN 9781849964715.

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

[11] Online 'Mendelian Inheritance in Man' (OMIM) APOE3 isoform, hyperlipoproteinemia, type III, autosomal recessive -107741#0015

[12] Online 'Mendelian Inheritance in Man' (OMIM) APOE3 isoform, APOE, CYS112 and ARG158 -107741#0001

[pmid16603077-13] Zuo L, van Dyck CH, Luo X, Kranzler HR, Yang BZ, Gelernter J (2006). "Variation at APOE and STH loci and Alzheimer's disease". Behavioral and Brain Functions 2 (1): 13. doi:10.1186/1744-9081-2-13. PMC 1526745. PMID 16603077.

[Meta-analysis-14] "Alzheimer Research Forum: Meta-Analyses of apolipoprotein E AD Association Studies".

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

[16] Breslow JL, Zannis VI, SanGiacomo TR, Third JL, Tracy T, Glueck CJ (Nov 1982). "Studies of familial type III hyperlipoproteinemia using as a genetic marker the apoE phenotype E2/2". Journal of Lipid Research 23 (8): 1224–35. PMID 7175379.

[17] Feussner G, Feussner V, Hoffmann MM, Lohrmann J, Wieland H, März W (1998). "Molecular basis of type III hyperlipoproteinemia in Germany". Human Mutation 11 (6): 417–23. doi:10.1002/(SICI)1098-1004(1998)11:6<417::AID-HUMU1>3.0.CO;2-5. PMID 9603433.

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[19] Huang X, Chen PC, Poole C (Jun 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.

[20] Federoff M, Jimenez-Rolando B, Nalls MA, Singleton AB (May 2012). "A large study reveals no association between APOE and Parkinson's disease". Neurobiology of Disease 46 (2): 389–92. doi:10.1016/j.nbd.2012.02.002. PMC 3323723. PMID 22349451.

[pmid3283935-21] Mahley RW (Apr 1988). "Apolipoprotein E: cholesterol transport protein with expanding role in cell biology". Science 240 (4852): 622–30. doi:10.1126/science.3283935. PMID 3283935.

[pmid8346443-22] Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW, Roses AD, Haines JL, Pericak-Vance MA (Aug 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.

[pmid8446617-23] Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (Mar 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): 1977–81. doi:10.1073/pnas.90.5.1977. PMC 46003. PMID 8446617.

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

[Cognitive_Impairment-25] Farlow MR, He Y, Tekin S, Xu J, Lane R, Charles HC (Nov 2004). "Impact of APOE in mild cognitive impairment". Neurology 63 (10): 1898–901. doi:10.1212/01.wnl.0000144279.21502.b7. PMID 15557508.

[26] Burt TD, Agan BK, Marconi VC, He W, Kulkarni H, Mold JE, Cavrois M, Huang Y, Mahley RW, Dolan MJ, McCune JM, Ahuja SK (Jun 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.

[27] Chapman J, Vinokurov S, Achiron A, Karussis DM, Mitosek-Szewczyk K, Birnbaum M, Michaelson DM, Korczyn AD (Feb 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.

[28] 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 (Mar 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.

[29] Friedman G, Froom P, Sazbon L, Grinblatt I, Shochina M, Tsenter J, Babaey S, Yehuda B, Groswasser Z (Jan 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.

[30] McCarron MO, Delong D, Alberts MJ (Oct 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.

[31] Kadotani H, Kadotani T, Young T, Peppard PE, Finn L, Colrain IM, Murphy GM, Mignot E (Jun 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.

[32] Gottlieb DJ, DeStefano AL, Foley DJ, Mignot E, Redline S, Givelber RJ, Young T (Aug 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.

[pmid23418430-33] Jacobs EG, Kroenke C, Lin J, Epel ES, Kenna HA, Blackburn EH, Rasgon NL (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.

[pmid18395206-34] Raber J (May 2008). "AR, apoE, and cognitive function". Hormones and Behavior 53 (5): 706–15. doi:10.1016/j.yhbeh.2008.02.012. PMC 2409114. PMID 18395206.

[pmid-21659554-35] Huebbe P, Nebel A, Siegert S, Moehring J, Boesch-Saadatmandi C, Most E, Pallauf J, Egert S, Müller MJ, Schreiber S, Nöthlings U, Rimbach G (Sep 2011). "APOE ε4 is associated with higher vitamin D levels in targeted replacement mice and humans". FASEB Journal 25 (9): 3262–70. doi:10.1096/fj.11-180935. PMID 21659554.

[36] Mondadori CR, de Quervain DJ, Buchmann A, Mustovic H, Wollmer MA, Schmidt CF, Boesiger P, Hock C, Nitsch RM, Papassotiropoulos A, Henke K (Aug 2007). "Better memory and neural efficiency in young apolipoprotein E epsilon4 carriers". Cerebral Cortex 17 (8): 1934–47. doi:10.1093/cercor/bhl103. PMID 17077159.

[37] Zhang Z, Mu J, Li J, Li W, Song J (Jan 2013). "Aberrant apolipoprotein E expression and cognitive dysfunction in patients with poststroke depression". Genetic Testing and Molecular Biomarkers 17 (1): 47–51. doi:10.1089/gtmb.2012.0253. PMID 23171142.

[38] Rogers JT, Weeber EJ (Aug 2008). "Reelin and apoE actions on signal transduction, synaptic function and memory formation". Neuron Glia Biology 4 (3): 259–70. doi:10.1017/S1740925X09990184. PMID 19674510.

[39] Jiang L, Zhong J, Dou X, Cheng C, Huang Z, Sun X (Aug 2015). "Effects of ApoE on intracellular calcium levels and apoptosis of neurons after mechanical injury". Neuroscience 301: 375–83. doi:10.1016/j.neuroscience.2015.06.005. PMID 26073697.

[40] 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 (Oct 2005). "Apolipoprotein-mediated pathways of lipid antigen presentation". Nature 437 (7060): 906–10. doi:10.1038/nature04001. PMID 16208376.

[pmid20182542-41] Zhang HL, Wu J, Zhu J (2010). "The role of apolipoprotein E in Guillain-Barré syndrome and experimental autoimmune neuritis". Journal of Biomedicine & Biotechnology 2010: 357412. doi:10.1155/2010/357412. PMC 2825561. PMID 20182542.

[pmid24244577-42] Braesch-Andersen S, Paulie S, Smedman C, Mia S, Kumagai-Braesch M (2013). "ApoE production in human monocytes and its regulation by inflammatory cytokines". PLOS ONE 8 (11): e79908. doi:10.1371/journal.pone.0079908. PMC 3828220. PMID 24244577.

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

[pmid1625800-44] Wisniewski T, Frangione B (Feb 1992). "Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid". Neuroscience Letters 135 (2): 235–8. doi:10.1016/0304-3940(92)90444-C. PMID 1625800.

[Neuron-45] 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 (Jun 2008). "ApoE promotes the proteolytic degradation of Abeta". Neuron (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-46] "Margaret Pericak-Vance, Ph.D.". Miami Institute of Human Genomics.

[pmid_2035524-47] Pericak-Vance MA, Bebout JL, Gaskell PC, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA (Jun 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.

[HauserRyan2013-48] Hauser PS, Ryan RO (Oct 2013). "Impact of apolipoprotein E on Alzheimer's disease". Current Alzheimer Research 10 (8): 809–17. doi:10.2174/15672050113109990156. PMC 3995977. PMID 23919769.

[pmid7920638-49] Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell PC, Rimmler JB, Locke PA, Conneally PM, Schmader KE (Jun 1994). "Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease". Nature Genetics 7 (2): 180–4. doi:10.1038/ng0694-180. PMID 7920638.

[ReferenceA-50] Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM (1997). "Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium". Jama 278 (16): 1349–56. doi:10.1001/jama.1997.03550160069041. PMID 9343467.

[pmid20210786-51] McNeill E, Channon KM, Greaves DR (Jun 2010). "Inflammatory cell recruitment in cardiovascular disease: murine models and potential clinical applications". Clinical Science 118 (11): 641–55. doi:10.1042/CS20090488. PMID 20210786.

リンク元	「アポE」「アポリポ蛋白E」「アポリポタンパクE」「アポリポ蛋白質E」
拡張検索	「apolipoprotein E receptor」「apolipoprotein E2」「apolipoprotein E4」「apolipoprotein E3」
関連記事	「apolipoprotein」「Es」「apolipoproteins」「E」

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案内

apolipoprotein E