apolipoprotein E (APOE)
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Function
- Apo E plays a significant role in chylomicron remnant & intermediate density lipoprotein (IDL) recognition & removal via LRP & the VLDL receptor, respectively
- Apo E also plays role in redistribution of cholesterol in membrane biosynthesis
- in all tissues, apo E is thought to function in the context of lipoprotein particles[7]
Structure
- glycoprotein with at least 4 polymorphic forms: apo E1, apo E2, apo E3, & apo E4
- isoforms differ from one another by a single charge
- the forms differ in number of Cys
- the substitute amino acid in most cases appears to be arginine.
- Apo E2 has 2 Cys, apo E3 1 Cys & apo E4 none
Expression
- Apo E is synthesized in the liver & enters the plasma as part of nascent HDL
- under the influence of lecithin cholesterol acyltransferase (LCAT), HDL accumulates cholesterol & apo E is transferred to VLDL & chylomicrons
- in contrast to most other apolipoproteins, apo E is also synthesized in cells outside of the enterohepatic system, including macrophages, adipocytes & astrocytes. [5, 6]; neurites are mentioned[1]
Pathology
- within the brain, apo E binds to the A4 amyloid peptide
- it is found within senile plaques
- ApoE signalling is also directly linked to dephosphorylation of tau & may protect against formation of paired helical filaments (PHF) & neurofibrillary tangles[8]
- polymorphism or defect in APOE are a cause of hyperlipoproteinemia type 3, most frequently apoE2/apoE2
- polymorphism in APOE, apoE4 allele, associated with Alzheimer disease type-2
- cortical thickness of the left entorhinal cortex is children is highest with apoE2 & lowest with apoE4[18]
- defects in APOE are a cause of sea-blue histiocytosis
- defects in APOE are a cause of lipoprotein glomerulopathy
Genetics
- the 3 major forms are the result of 3 independent alleles acting at a single gene locus; apoE2, apoE3, apoE4
- SNPs in apoE may be associated with human longevity[16][17]
Laboratory
- serum protein electrophorsis
Notes
- 1st isolated from plasma in 1972 & was originally known as arginine-rich apolipoprotein
More general terms
More specific terms
Additional terms
- apolipoprotein E genotype
- CD91, low density lipoprotein (LDL) receptor related protein (LRP) 1, apolipoprotein E [apoE] receptor 1, chylomicron remnant receptor or alpha-2 macroglobulin receptor
- very low-density lipoprotein receptor; VLDL receptor; VLDL-R (VLDLR)
References
- ↑ 1.0 1.1 OMIM https://mirror.omim.org/entry/107741
- ↑ Clinical Laboratory Medicine, Tilton et al (eds), Mosby Year Book, St. Louis, 1992, pg 129
- ↑ Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8446617
- ↑ Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA & Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993, pg 1023
- ↑ Laffitte BA, Repa JJ, Joseph SB, Wilpitz DC, Kast HR, Mangelsdorf DJ, Tontonoz P. LXRs control lipid-inducible expression of the apolipoprotein E gene in macrophages and adipocytes. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):507-12. Epub 2001 Jan 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11149950
- ↑ Pitas et al, Biochim Biophys Acta 917:148, 1987
- ↑ 7.0 7.1 Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11274343
- ↑ 8.0 8.1 Rampon C, Jiang CH, Dong H, Tang YP, Lockhart DJ, Schultz PG, Tsien JZ, Hu Y. Effects of environmental enrichment on gene expression in the brain. Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12880-4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11070096
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=348
- ↑ UniProt http://www.uniprot.org/uniprot/P02649.html
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/APOE
- ↑ SHMPD; Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=APOE
- ↑ Wikipedia; Note: apolipoprotein E entry http://en.wikipedia.org/wiki/apolipoprotein_E
- ↑ Protein Spotlight; Note: Tangled - Issue 83 of June 2007 http://web.expasy.org/spotlight/back_issues/sptlt083.shtm
- ↑ Strittmatter WJ et al Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1977-81 PMID: https://www.ncbi.nlm.nih.gov/pubmed/8446617
- ↑ 16.0 16.1 Sebastiani P et al Genetic signatures of exceptional longevity in humans. PLoS One. 2012;7(1):e29848. Epub 2012 Jan 18. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22279548
- ↑ 17.0 17.1 Soerensen M et al Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22234866
- ↑ 18.0 18.1 Shaw P, Lerch JP, Pruessner JC et al Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study. Lancet Neurol. 2007 Jun;6(6):494-500. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17509484
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=348
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:348
- OMIM: https://mirror.omim.org/entry/104310
- OMIM: https://mirror.omim.org/entry/107741
- OMIM: https://mirror.omim.org/entry/269600
- OMIM: https://mirror.omim.org/entry/611771
- UniProt: http://www.uniprot.org/uniprot/P02649.html