Apolipoprotein E: Difference between revisions

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===Alzheimer's disease===
===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.<ref>{{cite journal | vauthors = Sadigh-Eteghad S, Talebi M, Farhoudi M | title = Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer`s disease. A meta-analysis | journal = Neurosciences | volume = 17 | issue = 4 | pages = 321–6 | date = Oct 2012 | pmid = 23022896 }}</ref> "Nigerian blacks have the highest observed frequency of the APO E*4 allele in world populations."<ref name=":0">{{Cite journal|last=Sepehrnia|first=B.|last2=Kamboh|first2=M. I.|last3=Adams-Campbell|first3=L. L.|last4=Bunker|first4=C. H.|last5=Nwankwo|first5=M.|last6=Majumder|first6=P. P.|last7=Ferrell|first7=R. E.|date=1989-10-01|title=Genetic studies of human apolipoproteins. X. The effect of the apolipoprotein E polymorphism on quantitative levels of lipoproteins in Nigerian blacks|url=http://www.ncbi.nlm.nih.gov/pubmed/2491016|journal=American Journal of Human Genetics|volume=45|issue=4|pages=586–591|issn=0002-9297|pmc=1683508|pmid=2491016}}</ref> But AD is rare among them.<ref name=":0" /><ref>{{Cite journal|last=Notkola|first=I. L.|last2=Sulkava|first2=R.|last3=Pekkanen|first3=J.|last4=Erkinjuntti|first4=T.|last5=Ehnholm|first5=C.|last6=Kivinen|first6=P.|last7=Tuomilehto|first7=J.|last8=Nissinen|first8=A.|date=1998-01-01|title=Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease|url=http://www.ncbi.nlm.nih.gov/pubmed/9549720|journal=Neuroepidemiology|volume=17|issue=1|pages=14–20|issn=0251-5350|pmid=9549720}}</ref> 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]].<ref name="pmid1625800">{{cite journal | vauthors = Wisniewski T, Frangione B | title = Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid | journal = Neuroscience Letters | volume = 135 | issue = 2 | pages = 235–8 | date = Feb 1992 | pmid = 1625800 | doi = 10.1016/0304-3940(92)90444-C }}</ref> 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.<ref name="Neuron">{{cite journal | vauthors = 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 | title = ApoE promotes the proteolytic degradation of Abeta | journal = Neuron | volume = 58 | issue = 5 | pages = 681–93 | date = Jun 2008 | pmid = 18549781 | pmc = 2493297 | doi = 10.1016/j.neuron.2008.04.010 | publisher = Cell Press | laydate = 2008-06-13 | laysource = ScienceDaily | laysummary = http://www.sciencedaily.com/releases/2008/06/080611135123.htm }}</ref>
The E4 variant is the largest known genetic risk factor for late-onset sporadic [[Alzheimer's disease]] (AD) in a variety of ethnic groups.<ref>{{cite journal | vauthors = Sadigh-Eteghad S, Talebi M, Farhoudi M | title = Association of apolipoprotein E epsilon 4 allele with sporadic late onset Alzheimer`s disease. A meta-analysis | journal = Neurosciences | volume = 17 | issue = 4 | pages = 321–6 | date = Oct 2012 | pmid = 23022896 }}</ref> "Nigerian blacks have the highest observed frequency of the APO E*4 allele in world populations."<ref name=":0">{{Cite journal|last=Sepehrnia|first=B.|last2=Kamboh|first2=M. I.|last3=Adams-Campbell|first3=L. L.|last4=Bunker|first4=C. H.|last5=Nwankwo|first5=M.|last6=Majumder|first6=P. P.|last7=Ferrell|first7=R. E.|date=1989-10-01|title=Genetic studies of human apolipoproteins. X. The effect of the apolipoprotein E polymorphism on quantitative levels of lipoproteins in Nigerian blacks|url=http://www.ncbi.nlm.nih.gov/pubmed/2491016|journal=American Journal of Human Genetics|volume=45|issue=4|pages=586–591|issn=0002-9297|pmc=1683508|pmid=2491016}}</ref> But AD is rare among them.<ref name=":0" /><ref name=":1">{{Cite journal|last=Notkola|first=I. L.|last2=Sulkava|first2=R.|last3=Pekkanen|first3=J.|last4=Erkinjuntti|first4=T.|last5=Ehnholm|first5=C.|last6=Kivinen|first6=P.|last7=Tuomilehto|first7=J.|last8=Nissinen|first8=A.|date=1998-01-01|title=Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease|url=http://www.ncbi.nlm.nih.gov/pubmed/9549720|journal=Neuroepidemiology|volume=17|issue=1|pages=14–20|issn=0251-5350|pmid=9549720}}</ref> There is growing evidence that suggests that this may be due to their low cholesterol levels.<ref name=":0" /><ref name=":1" /><ref>{{Cite journal|last=Petanceska|first=Suzana S.|last2=DeRosa|first2=Steven|last3=Sharma|first3=Ali|last4=Diaz|first4=Nichole|last5=Duff|first5=Karen|last6=Tint|first6=Steven G.|last7=Refolo|first7=Lorenzo M.|last8=Pappolla|first8=Miguel|date=2003-01-01|title=Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol|url=http://www.ncbi.nlm.nih.gov/pubmed/14501024|journal=Journal of molecular neuroscience: MN|volume=20|issue=3|pages=395–406|doi=10.1385/JMN:20:3:395|issn=0895-8696|pmid=14501024}}</ref><ref>{{Cite journal|last=Kivipelto|first=Miia|last2=Helkala|first2=Eeva-Liisa|last3=Laakso|first3=Mikko P.|last4=Hänninen|first4=Tuomo|last5=Hallikainen|first5=Merja|last6=Alhainen|first6=Kari|last7=Iivonen|first7=Susan|last8=Mannermaa|first8=Arto|last9=Tuomilehto|first9=Jaakko|date=2002-08-06|title=Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease|url=http://www.ncbi.nlm.nih.gov/pubmed/12160362|journal=Annals of Internal Medicine|volume=137|issue=3|pages=149–155|issn=1539-3704|pmid=12160362}}</ref> 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]].<ref name="pmid1625800">{{cite journal | vauthors = Wisniewski T, Frangione B | title = Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid | journal = Neuroscience Letters | volume = 135 | issue = 2 | pages = 235–8 | date = Feb 1992 | pmid = 1625800 | doi = 10.1016/0304-3940(92)90444-C }}</ref> 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.<ref name="Neuron">{{cite journal | vauthors = 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 | title = ApoE promotes the proteolytic degradation of Abeta | journal = Neuron | volume = 58 | issue = 5 | pages = 681–93 | date = Jun 2008 | pmid = 18549781 | pmc = 2493297 | doi = 10.1016/j.neuron.2008.04.010 | publisher = Cell Press | laydate = 2008-06-13 | laysource = ScienceDaily | laysummary = http://www.sciencedaily.com/releases/2008/06/080611135123.htm }}</ref>


The pivotal role of ''ApoE'' in AD was first identified through linkage analysis by Margaret Pericak-Vance<ref name="urlMiami Institute of Human Genomics - People">{{cite web | url = http://www.mihg.org/weblog/people/2007/11/margaret-pericakvance-phd.html | title = Margaret Pericak-Vance, Ph.D. | author = | authorlink = | coauthors = | date = | work = | publisher = Miami Institute of Human Genomics | pages = | archiveurl = | archivedate = | quote = | accessdate = }}</ref> while working in the Roses lab at [[Duke University]]<ref name="pmid 2035524">{{cite journal | vauthors = Pericak-Vance MA, Bebout JL, Gaskell PC, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA | title = Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage | journal = American Journal of Human Genetics | volume = 48 | issue = 6 | pages = 1034–50 | date = Jun 1991 | pmid = 2035524 | pmc = 1683100 | doi = }}</ref> Linkage studies were followed by association analysis confirming the role of the ApoE4 allele as a strong genetic risk factor for AD.<ref name="pmid8346443"/><ref name="pmid8446617"/>
The pivotal role of ''ApoE'' in AD was first identified through linkage analysis by Margaret Pericak-Vance<ref name="urlMiami Institute of Human Genomics - People">{{cite web | url = http://www.mihg.org/weblog/people/2007/11/margaret-pericakvance-phd.html | title = Margaret Pericak-Vance, Ph.D. | author = | authorlink = | coauthors = | date = | work = | publisher = Miami Institute of Human Genomics | pages = | archiveurl = | archivedate = | quote = | accessdate = }}</ref> while working in the Roses lab at [[Duke University]]<ref name="pmid 2035524">{{cite journal | vauthors = Pericak-Vance MA, Bebout JL, Gaskell PC, Yamaoka LH, Hung WY, Alberts MJ, Walker AP, Bartlett RJ, Haynes CA, Welsh KA | title = Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage | journal = American Journal of Human Genetics | volume = 48 | issue = 6 | pages = 1034–50 | date = Jun 1991 | pmid = 2035524 | pmc = 1683100 | doi = }}</ref> Linkage studies were followed by association analysis confirming the role of the ApoE4 allele as a strong genetic risk factor for AD.<ref name="pmid8346443"/><ref name="pmid8446617"/>

Revision as of 23:56, 5 July 2016

APOE
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesAPOE, AD2, APO-E, LDLCQ5, LPG, apolipoprotein E, ApoE4
External IDsOMIM: 107741 MGI: 88057 HomoloGene: 30951 GeneCards: APOE
Orthologs
SpeciesHumanMouse
Entrez

348

11816

Ensembl

ENSG00000130203

ENSMUSG00000002985

UniProt

P02649

P08226

RefSeq (mRNA)

NM_001302691
NM_000041
NM_001302688
NM_001302689
NM_001302690

NM_009696
NM_001305819
NM_001305843
NM_001305844

RefSeq (protein)

NP_000032
NP_001289617
NP_001289618
NP_001289619
NP_001289620

NP_001292748
NP_001292772
NP_001292773
NP_033826

Location (UCSC)Chr 19: 44.91 – 44.91 MbChr 7: 19.43 – 19.43 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5] 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.[6] APOE is the principal cholesterol carrier in the brain.[7] This protein is involved in Alzheimer’s disease and cardiovascular disease.[8]

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.[9] In melanocytic cells APOE gene expression may be regulated by MITF.[10]

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.[11]

Polymorphisms

APOE is polymorphic,[12][13] with three major alleles: ApoE2 (cys112, cys158), ApoE3 (cys112, arg158), and ApoE4 (arg112, arg158).[8][14][15] Although these allelic forms differ from each other by only one or two amino acids at positions 112 and 158,[16][17][18] these differences alter APOE structure and function. These have physiological consequences:

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.[41]

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.[14] 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.[42] There are seven currently identified mammalian receptors for APOE which belong to the evolutionarily conserved LDLR family.[43]

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.[5] 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.[8] 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.[44]

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) [45] to natural killer T cell as well as modulation of inflammation and oxidation.[46] 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.[47]

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.[48] "Nigerian blacks have the highest observed frequency of the APO E*4 allele in world populations."[49] But AD is rare among them.[49][50] There is growing evidence that suggests that this may be due to their low cholesterol levels.[49][50][51][52] 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.[53] 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.[54]

The pivotal role of ApoE in AD was first identified through linkage analysis by Margaret Pericak-Vance[55] while working in the Roses lab at Duke University[56] Linkage studies were followed by association analysis confirming the role of the ApoE4 allele as a strong genetic risk factor for AD.[27][28]

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.[57] There is also evidence that the ApoE2 allele may serve a protective role in AD.[58] 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.[59]

Estimated worldwide human allele frequencies of ApoE * in Caucasian population[59]
Allele ε2 ε3 ε4
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.[60]

Interactions

Interactive pathway map

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

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Statin_Pathway_WP430go to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to articlego to article
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Statin pathway edit
  1. ^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000130203 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000002985 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: APOE apolipoprotein E".
  6. ^ Liu CC, Liu CC, Kanekiyo T, Xu H, Bu G (Feb 2013). "Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy". Nature Reviews. Neurology. 9 (2): 106–18. doi:10.1038/nrneurol.2012.263. PMID 23296339.
  7. ^ Puglielli, Luigi; Tanzi, Rudolph E.; Kovacs, Dora M. (2003-04-01). "Alzheimer's disease: the cholesterol connection". Nature Neuroscience. 6 (4): 345–351. doi:10.1038/nn0403-345. ISSN 1097-6256.
  8. ^ a b c (ed.), Ian P. Stolerman (2010). Encyclopedia of psychopharmacology (Online-Ausg. ed.). Berlin: Springer. ISBN 9783540686989. {{cite book}}: |last1= has generic name (help)
  9. ^ 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.
  10. ^ 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.
  11. ^ Phillips MC (Sep 2014). "Apolipoprotein E isoforms and lipoprotein metabolism". IUBMB Life. 66 (9): 616–23. doi:10.1002/iub.1314. PMID 25328986.
  12. ^ 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.
  13. ^ 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.
  14. ^ a b Baars, H.F.; van der Smagt, J.J.; Doevandans, P.A.F.M. (2011). Clinical Cardiogenetics. London: Springer. ISBN 9781849964715. {{cite book}}: Unknown parameter |name-list-format= ignored (|name-list-style= suggested) (help)
  15. ^ 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.
  16. ^ Online Mendelian Inheritance in Man (OMIM): APOE3 isoform, hyperlipoproteinemia, type III, autosomal recessive - 107741#0015
  17. ^ Online Mendelian Inheritance in Man (OMIM): APOE3 isoform, APOE, CYS112 and ARG158 - 107741#0001
  18. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  19. ^ a b c "Alzheimer Research Forum: Meta-Analyses of apolipoprotein E AD Association Studies".
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ Civeira F, Pocoví M, Cenarro A, Casao E, Vilella E, Joven J, González J, Garcia-Otín AL, Ordovás JM (Dec 1996). "Apo E variants in patients with type III hyperlipoproteinemia". Atherosclerosis. 127 (2): 273–82. doi:10.1016/S0021-9150(96)05969-2. PMID 9125318.
  24. ^ 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.
  25. ^ 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.
  26. ^ 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.
  27. ^ a b 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.
  28. ^ a b 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.
  29. ^ 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.
  30. ^ a b 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.
  31. ^ 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.
  32. ^ 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.
  33. ^ 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.
  34. ^ 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.
  35. ^ 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.
  36. ^ 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.
  37. ^ 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.
  38. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  39. ^ 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.
  40. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  41. ^ 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.
  42. ^ 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.
  43. ^ 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.
  44. ^ 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.
  45. ^ 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.
  46. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  47. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  48. ^ 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.
  49. ^ a b c Sepehrnia, B.; Kamboh, M. I.; Adams-Campbell, L. L.; Bunker, C. H.; Nwankwo, M.; Majumder, P. P.; Ferrell, R. E. (1989-10-01). "Genetic studies of human apolipoproteins. X. The effect of the apolipoprotein E polymorphism on quantitative levels of lipoproteins in Nigerian blacks". American Journal of Human Genetics. 45 (4): 586–591. ISSN 0002-9297. PMC 1683508. PMID 2491016.
  50. ^ a b Notkola, I. L.; Sulkava, R.; Pekkanen, J.; Erkinjuntti, T.; Ehnholm, C.; Kivinen, P.; Tuomilehto, J.; Nissinen, A. (1998-01-01). "Serum total cholesterol, apolipoprotein E epsilon 4 allele, and Alzheimer's disease". Neuroepidemiology. 17 (1): 14–20. ISSN 0251-5350. PMID 9549720.
  51. ^ Petanceska, Suzana S.; DeRosa, Steven; Sharma, Ali; Diaz, Nichole; Duff, Karen; Tint, Steven G.; Refolo, Lorenzo M.; Pappolla, Miguel (2003-01-01). "Changes in apolipoprotein E expression in response to dietary and pharmacological modulation of cholesterol". Journal of molecular neuroscience: MN. 20 (3): 395–406. doi:10.1385/JMN:20:3:395. ISSN 0895-8696. PMID 14501024.
  52. ^ Kivipelto, Miia; Helkala, Eeva-Liisa; Laakso, Mikko P.; Hänninen, Tuomo; Hallikainen, Merja; Alhainen, Kari; Iivonen, Susan; Mannermaa, Arto; Tuomilehto, Jaakko (2002-08-06). "Apolipoprotein E epsilon4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease". Annals of Internal Medicine. 137 (3): 149–155. ISSN 1539-3704. PMID 12160362.
  53. ^ 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.
  54. ^ 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. 58 (5). Cell Press: 681–93. doi:10.1016/j.neuron.2008.04.010. PMC 2493297. PMID 18549781. {{cite journal}}: Unknown parameter |laydate= ignored (help); Unknown parameter |laysource= ignored (help); Unknown parameter |laysummary= ignored (help)
  55. ^ "Margaret Pericak-Vance, Ph.D." Miami Institute of Human Genomics. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  56. ^ 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.
  57. ^ 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.
  58. ^ 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.
  59. ^ a b 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.
  60. ^ 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.

Further reading

External links

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