Apolipoprotein E

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Apolipoprotein E(APOE, apoE) is an interesting membrane is 34 kDa membrane protein involved in cholesterol transport and cellular homeostasis. There is a differential risk associated with the four common human alleles (ε1,ε2,ε3, ε4) in a number of neurodegenerative diseases, including dementia, glaucoma and of course atherosclerosis.

In neurons apoE

It may have its differential activity indirectly as the ApoE receptor 2 (Apoer2), is essential for protection against neuronal cell loss.[1]

Whole population screening for such a polygenetic risk factor is ineffectual[2]. However the following data may help in advising patients and doctors why this is so for Alzheimer's disease(AD).

  • No family history of AD, the epidemiologic/actuarial lifetime risk of AD is about 15%.
  • Lifetime risk of such individuals with one APOE ε4 allele is 29%
  • Lifetime risk of such individuals with no APOE ε4 allele is 9%[3]

So doubling or halving the relative risk makes little difference to forward planning when you still have a 10% residual risk. The question of screening in isolated populations is still very questionable as 55% of Alzheimer's cases remain unexplained[4]

Associations

No association

  • Age-related macular degeneration[14] (contrary to earlier reports but ε4 may delay detection of disease [15])
  • Risk of carotid plaque formation in woman[16]
  • Ischaemic stroke (except subpopulations as above)[17]

References

  1. ↑ Beffert U, Nematollah Farsian F, Masiulis I, Hammer RE, Yoon SO, Giehl KM, et al. ApoE Receptor 2 Controls Neuronal Survival in the Adult Brain. Current biology : CB 2006;16:2446-52. (Direct link – subscription may be required.)
  2. ↑ Devanand DP, Pelton GH, Zamora D, Liu X, Tabert MH, Goodkind M, et al. Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Archives of neurology 2005;62:975-80. (Direct link – subscription may be required.)
  3. ↑ Seshadri S, Drachman DA, Lippa CF. Apolipoprotein E epsilon 4 allele and the lifetime risk of Alzheimer's disease. What physicians know, and what they should know. Archives of neurology 1995;52:1074-9.
  4. ↑ Sleegers K, Roks G, Theuns J, Aulchenko YS, Rademakers R, Cruts M, et al. Familial clustering and genetic risk for dementia in a genetically isolated Dutch population. Brain : a journal of neurology 2004;127:1641-9. (Direct link – subscription may be required.)
  5. ↑ Jurkovicova D, Goncalvesova E, Sedlakova B, Hudecova S, Fabian J, Krizanova O. Is the ApoE polymorphism associated with dilated cardiomyopathy? General physiology and biophysics 2006;25:3-10.
  6. ↑ Farrer LA, Cupples LA, Haines JL, Hyman B, Kukull WA, Mayeux R, Myers RH, Pericak-Vance MA, Risch N, van Duijn CM. 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. 1997;278(16):1349-56.
  7. ↑ Beffert U, Nematollah Farsian F, Masiulis I, Hammer RE, Yoon SO, Giehl KM, et al. ApoE Receptor 2 Controls Neuronal Survival in the Adult Brain. Current biology : CB 2006;16:2446-52. (Direct link – subscription may be required.)
  8. ↑ Hsu CC, Kao WH, Coresh J, Pankow JS, Marsh-Manzi J, Boerwinkle E, et al. Apolipoprotein E and progression of chronic kidney disease. JAMA : the journal of the American Medical Association 2005;293:2892-9. (Direct link – subscription may be required.)
  9. ↑ Beilby JP, Hunt CC, Palmer LJ, Chapman CM, Burley JP, McQuillan BM, et al. Apolipoprotein E gene polymorphisms are associated with carotid plaque formation but not with intima-media wall thickening: results from the Perth Carotid Ultrasound Disease Assessment Study (CUDAS). Stroke; a journal of cerebral circulation 2003;34:869-74. (Direct link – subscription may be required.)
  10. ↑ Banerjee I, Gupta V, Ganesh S.Association of gene polymorphism with genetic susceptibility to stroke in Asian populations: a meta-analysis. J Hum Genet. 2006 Dec 14;
  11. ↑ Lam CY, Fan BJ, Wang DY, Tam PO, Yung Tham CC, Leung DY, et al. Association of apolipoprotein E polymorphisms with normal tension glaucoma in a Chinese population. Journal of glaucoma 2006;15:218-22. (Direct link – subscription may be required.)
  12. ↑ Pinholt M, Frederiksen JL, Christiansen M. The association between apolipoprotein E and multiple sclerosis. Eur J Neurol. 2006;13(6):573-80.
  13. ↑ Boland LL, Folsom AR, Boerwinkle E; Atherosclerosis Risk in Communities (Aric) Study Investigators. Apolipoprotein E genotype and gallbladder disease risk in a large population-based cohort. Ann Epidemiol. 2006;16(10):763-9.
  14. ↑ Wong TY, Shankar A, Klein R, Bray MS, Couper DJ, Klein BE, et al. Apolipoprotein E gene and early age-related maculopathy: the Atherosclerosis Risk in Communities Study. Ophthalmology 2006;113:255-9. (Direct link – subscription may be required.)
  15. ↑ Baird PN, Guida E, Chu DT, Vu HT, Guymer RH. The epsilon2 and epsilon4 alleles of the apolipoprotein gene are associated with age-related macular degeneration. Investigative ophthalmology & visual science 2004;45:1311-5.
  16. ↑ Beilby JP, Hunt CC, Palmer LJ, Chapman CM, Burley JP, McQuillan BM, et al. Apolipoprotein E gene polymorphisms are associated with carotid plaque formation but not with intima-media wall thickening: results from the Perth Carotid Ultrasound Disease Assessment Study (CUDAS). Stroke; a journal of cerebral circulation 2003;34:869-74. (Direct link – subscription may be required.)
  17. ↑ Casas JP, Hingorani AD, Bautista LE, Sharma P. Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Archives of neurology 2004;61:1652-61. (Direct link – subscription may be required.)
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