Skip to main content
SpringerLink
Log in

Genetic Association between the Apolipoprotein E (APOE) Gene and Different Forms of Alzheimer's Disease

  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

Allele ε4of the apolipoprotein E (APOE) gene is associated with higher risk for family or sporadic Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOEallele and genotype frequency distributions were evaluated in 207 AD patients without vascular disorders, 62 AD patients with vascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele ε4in patients with early-onset and late-onset AD was three times higher than in controls (P< 0.000001). The increase in the frequency of ε4in mixed dementia cases over controls was somewhat less but still significant (P= 0.0019). Relative risk of AD in carriers of allele ε4was five times higher than in carriers of alleles ε2and ε3(P< 0.000001). Allele ε2showed evidence of a protective effect in the early-onset AD group (P= 0.015). These results suggest that APOEallele ε4is a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. St. George-Hyslop, P.H., Tanzi, R.E., Polinsky, R.J., et al., The Genetic Defect Causing Familial Alzheimer Disease Maps on Chromosome 21, Science, 1987, vol. 235, pp. 885-889.

    Google Scholar 

  2. Hardy, J., Amyloid and the Presenilins in Alzheimer's Disease, TINS, 1997, vol. 20, pp. 154-159.

    Google Scholar 

  3. Goate, A., Chartier-Harlin, M.C., Mullan, M., et al., Segregation of a Missense Mutation in the Amyloid Precursor Protein Gene with Familial Alzheimer's Disease, Nature, 1991, vol. 349, pp. 704-706.

    Google Scholar 

  4. Sherington, R., Rogaev, E., Liang, Y., et al., Cloning of a Gene Bearing Missense Mutations in Early-Onset Familial Alzheimer's Disease, Nature, 1995, vol. 375, pp. 754-760.

    Google Scholar 

  5. Rogaev, E., Sherington, R., Rogaeva, E., et al., Analysis of the 5'-Sequence, Genomic Structure, and Alternative Splicing of the Presenilin 1 Gene Associated with Early-Onset Alzheimer's Disease, Genomics, 1997, vol. 40, pp. 415-424.

    Google Scholar 

  6. Rogaev, E., Sherington, R., Rogaeva, E., et al., Familial Alzheimer's Disease in Kindreds with Missense Mutations in a Gene on Chromosome 1 Related to the Alzheimer's Disease Type 3 Gene, Nature, 1995, vol. 376, pp. 775-778.

    Google Scholar 

  7. Levy-Lahad, E., Wasco, E., Poorkaj, P., et al., Candidate Gene for the Chromosome 1 Familial Alzheimer's Disease Locus, Science, 1995, vol. 269, pp. 973-977.

    Google Scholar 

  8. Mahley, R.W., Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology, Science, 1988, vol. 240, pp. 622-630.

    Google Scholar 

  9. Beisiegel, U., Weber, W., Ihrke, G., et al., The LDLReceptor-Related Protein, LRR, Is an Apolipoprotein E-Binding Protein, Nature, 1989, vol. 341, pp. 162-164.

    Google Scholar 

  10. Lambert, J.C., Pasquier, F., Cottel, D., et al., A New Polymorphism in the APOE Promoter Associated with Risk of Developing Alzheimer's Disease, Hum. Mol. Genet., 1998, vol. 7, pp. 533-540.

    Google Scholar 

  11. Bullido, M.J., Artiga, M.J., Recuero, M., et al., A Polymorphism in the Regulatory Region of APOE Associated with Risk for Alzheimer's Dementia, Nat. Genet., 1998, vol. 18, pp. 69-71.

    Google Scholar 

  12. Roses, A.D., Apolipoprotein E Genotyping in the Differential Diagnosis, Not Prediction, of Alzheimer's Disease, Ann. Neurol., 1995, vol. 38, pp. 6-14.

    Google Scholar 

  13. Corbo, R.M. and Scacchi, R., Apolipoprotein E (APOE) Allele Distribution in the World: Is APOE*4 a “Thrifty” Allele?, Ann. Hum. Genet., 1999, vol. 63, pp. 301-310.

    Google Scholar 

  14. St. George-Hyslop, P.H., Molecular Genetics of Alzheimer's Disease, Biol. Psyhiatr., 2000, vol. 47, pp. 183-199.

    Google Scholar 

  15. Saunders, A.M., Strittmatter, W.J., Schmechel, D., et al., Association of Apolipoprotein E Allele ?4 with Late-Onset Familial and Sporadic Alzheimer's Disease, Neurology, 1993, vol. 43, pp. 1467-1472.

    Google Scholar 

  16. Rebeck, G.W., Reiter, J.S., Strickland, K., et al., Apolipoprotein E in Sporadic Alzheimer's Disease: Allelic Variation and Receptor Interaction, Neuron, 1993, vol. 11, pp. 575-580.

    Google Scholar 

  17. Corder, E.N., Saunders, A.M., Strittmatter, W.J., et al., Gene Dose of Apolipoprotein E Type 4 Allele and Risk of Alzheimer's Disease in Late-Onset Families, Science, 1993, vol. 261, pp. 921-923.

    Google Scholar 

  18. Nalbantoglu, J., Gilfix, B.M., Bertrand, P., et al., Predictive Value of Apolipoprotein E Genotyping in Alzheimer's Disease: Results of an Autopsy Series and an Analysis of Combined Studies, Ann. Neurol., 1994, vol. 36, pp. 889-895.

    Google Scholar 

  19. Roses, A.D., Devin, B., Conneally, P.M., et al., Measuring the Genetic Contribution of APOE in Late-Onset Alzheimer's Disease, Am. Hum. Genet., 1995, vol. 57, abstract A202.

  20. Strittmatter, W.J., Saunders, A.M., Schmechel, D., et al., Apolipoprotein E: High-Avidity Binding to β-Amyloid and Increased Frequency of Type 4 Allele in Late-Onset Familial Alzheimer's Disease, Proc. Natl. Acad. Sci. USA, 1993, vol. 90, pp. 1977-1981.

    Google Scholar 

  21. Huang, D.Y., Goedert, M., Jakes, R., et al., Isoform-Specific Interactions of Apolipoprotein E with the Microtubule-Associated Protein MAP2c: Implications for Alzheimer's Disease, Neurosci. Lett., 1994, vol. 182, pp. 55-58.

    Google Scholar 

  22. Strittmatter, W.J., Saunders, A.M., Goedert, M., et al., Isoform-Specific Interactions of Apolipoprotein E with the Microtubule-Associated Protein TAU: Implications for Alzheimer's Disease, Proc. Natl. Acad. Sci. USA, 1994, vol. 91, pp. 11 183-11 186.

    Google Scholar 

  23. Farrer, L.A., Genetics and the Dementia Patient, Neurologist, 1997, vol. 3, pp. 13-30.

    Google Scholar 

  24. Sayi, J.G., Patel, N.B., Premkumar, D.R., et al., Apolipoprotein E Polymorphism in Elderly East Africans, East Afr. Med. J., 1997, vol. 74, pp. 668-670.

    Google Scholar 

  25. Hendrie, H.C., Hall, K.S., Hui, S., et al., Apolipoprotein E Genotypes and Alzheimer's Disease in a Community Study of Elderly African Americans, Ann. Neurol., 1995, vol. 37, pp. 118-120.

    Google Scholar 

  26. Tang, M.X., Stern, Y., Marder, K., et al., The APOE ε4 Allele and Risk of Alzheimer's Disease among African Americans, Whites, and Hispanics, JAMA, 1998, vol. 279, pp. 751-755.

    Google Scholar 

  27. Breteler, M.M.B., Claus, J.J., van Duijn, C.M., et al., Epidemiology of Alzheimer's Disease, Epidemiol. Rev., 1992, vol. 14, pp. 59-82.

    Google Scholar 

  28. Gavrilova, S.I. and Kalyn, A.B., Prevalence of Age-Related Dementia in an Elderly Population of Moscow, Int. Conf. on Aging, Depression, and Dementia, Bern: Springer-Verlag, 1994, pp. 85-89.

    Google Scholar 

  29. Hixson, J.E. and Vernier, D.T., Restriction Isotyping of Human Apolipoprotein E by Gene Amplification and Cleavage with HhaI, J. Lipid Res., 1990, vol. 31, pp. 545-548.

    Google Scholar 

  30. Maestre, G., Schofleld, P., Chun, M., et al., Ethnic Variation in the Association between APOE-ε4 and Alzheimer's Disease: Follow-Up Study, in Apolipoprotein E and Alzheimer's Disease, Berlin: Springer-Verlag, 1996, pp. 170-179.

    Google Scholar 

  31. Kuusisto, J., Koivisto, K., Kervinen, K., et al., Association of Apolipoprotein E Phenotypes with Late-Onset Alzheimer's Disease: Population Based Study, Brit. Med. J., 1994, vol. 309, pp. 636-638.

    Google Scholar 

  32. Pericak-Vance, M., Johnson, C., Rimmler, J., et al., Alzheimer's Disease and Apolipoprotein E-4 Allele in an Amish Population, Ann. Neurol., 1996, vol. 39, pp. 700-704.

    Google Scholar 

  33. Schachter, F., Faure-Delanef, L., Guenot, F., et al., Genetic Associations with Human Longevity at the APOE and ACE Loci, Nat. Genet., 1994, vol. 6, pp. 29-32.

    Google Scholar 

  34. Corder, E.H., Saunders, A.M., Risch, N.J., et al., Protective Effect of Apolipoprotein E Type 2 Allele for Late Onset Alzheimer's Disease, Nat. Genet., 1994, vol. 7, pp. 180-184.

    Google Scholar 

  35. Rebeck, G.W., Perls, T.T., West, H.L., et al., Reduced Apolipoprotein E ε4 Allele Frequency in the Oldest Old Alzheimer's Patients and Cognitively Normal Individuals, Neurology, 1994, vol. 44, pp. 1513-1516.

    Google Scholar 

  36. Van Duijn, C.M., de Knijff, P., Cruts, M., et al., Apolipoprotein E Allele in Population-Based Study of Early-Onset Alzheimer's Disease, Nat. Genet., 1994, vol. 7, pp. 74-78.

    Google Scholar 

  37. Premkumar, D.R.D., Cohen, D.L., Hedera, P., et al., Apolipoprotein E ε4 Allele in Cerebral Amyloid Angiopathy and Cerebrovascular Pathology Associated with Alzheimer's Disease, Am. J. Pathol., 1996, vol. 148, pp. 2083-2095.

    Google Scholar 

  38. Cumming, A.M. and Robertson, F., Polymorphism at the APOE Locus in Relation to Risk of Coronary Heart Disease, Clin. Genet., 1984, vol. 25, pp. 310-313.

    Google Scholar 

  39. Blacker, D., Wilcox, M.A., Laird, N.M., et al., α-2 Macroglobulin Is Genetically Associated with Alzheimer's Disease, Nat. Genet., 1998, vol. 19, pp. 357-360.

    Google Scholar 

  40. Korovaitseva, G., Premkumar, S., Grigorenco, A., et al., α-2 Macroglobulin Gene in Early-and Late-Onset Alzheimer's Disease, Neurosci. Lett., 1999, vol. 271, pp. 129-131.

    Google Scholar 

  41. Farrer, L.A., Sherbatich, T., Keryanov, S., Korovaitseva, G., et al., Association between Angiotensin-Converting Enzyme and Alzheimer's Disease, Arch. Neurol., 2000, vol. 5, pp. 210-214.

    Google Scholar 

  42. Kehoe, P.G., Russ, G., Mcilray, S., et al., Variation in DCP1, Encoding ACE, Is Associated with Susceptibility to Alzheimer's Disease, Nat. Genet., 1999, vol. 21, pp. 71-72.

    Google Scholar 

  43. Chapman, J., Wang, M., Treves, T.A., et al., ACE, MTHFR, Factor V. Leiden, and APOE Polymorphisms in Patients with Vascular and Alzheimer's Dementia, Stroke, 1998, vol. 29, pp. 1401-1404.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, 113152, Russia

    G. I. Korovaitseva, T. V. Sherbatich, N. V. Selezneva, S. I. Gavrilova, V. E. Golimbet, N. I. Voskresenskaya & E. I. Rogaev

  2. Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia

    T. V. Sherbatich

Authors
  1. G. I. Korovaitseva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. V. Sherbatich
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. V. Selezneva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. I. Gavrilova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. E. Golimbet
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. I. Voskresenskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E. I. Rogaev
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Korovaitseva, G.I., Sherbatich, T.V., Selezneva, N.V. et al. Genetic Association between the Apolipoprotein E (APOE) Gene and Different Forms of Alzheimer's Disease. Russian Journal of Genetics 37, 422–427 (2001). https://doi.org/10.1023/A:1016610727938

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1016610727938

Keywords

Search

Navigation