Skip to main content
May 1, 1997

Alzheimer's disease: Clinical implications of the apolipoprotein E genotype

May 1997 issue
48 (5_suppl_6) 30S-34S


Article abstract-Inheritance of the apolipoprotein E (APOE = gene; apoE = protein) epsilon 4 gene is associated with a higher risk for development of Alzheimer's disease (AD) and for occurrence of this illness at a younger age. APOE gene dose and genotype interact with gender, ethnicity, and age to influence the probability of developing AD, as well as the rate of disease progression. The sensitivity and specificity of APOE genotyping, however, and the longer-term implications of the epsilon 4 allele as a susceptibility factor for AD, are not yet adequately understood to recommend the use of APOE genotyping in genetic counseling of asymptomatic family members of AD patients. Insufficient evidence also exists at this time to recommend APOE genotyping as an adjuvant for the differential diagnosis of dementia or as a possible predictor for response to drug therapy. These potential future clinical indications for apoE genotyping are under active investigation.
NEUROLOGY 1997;48(Suppl 6): S30-S34

Get full access to this article

View all available purchase options and get full access to this article.


Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late-onset families. Science 1993;261:921-923.
Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. Neurology 1993;43:1467-1472.
Poirier J, Davignon J, Bouthillier D, Kogan S, Bertrand P, Gauthier S. Apolipoprotein E polymorphism and Alzheimer's disease. Lancet 1993;342:697-699.
Tsai M-S, Tangalos EG, Petersen RC, et al. Apolipoprotein E: risk factor for Alzheimer disease. Am J Hum Genet 1994;54:643-649.
Lucotte G, Turpin J-C, Landais P. Apolipoprotein E-epsilon 4 allele doses in late-onset Alzheimer's disease. Ann Neurol 1994;36:681-682.
Mayeux R, Stern Y, Ottman R, et al. The apolipoprotein epsilon 4 allele in patients with Alzheimer's disease. Ann Neurol 1993;34:752-754.
Liddell M, Williams J, Bayer A, Kaiser F, Owen M. Confirmation of association between the epsilon 4 allele of apolipoprotein E and Alzheimer's disease. J Med Genet 1994;31:197-200.
Brousseau T, Legrain S, Berr C, Gourlet V, Vidal O, Amouyel P. Confirmation of the epsilon 4 allele of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease. Neurology 1994;44:342-344.
Jarvik GP, Larson EB, Goddard K, Kukull WA, Schellenberg GD, Wijsman EM. Influence of apolipoprotein E genotype on the transmission of Alzheimer's disease in a community-based sample. Am J Hum Genet 1996;58:191-200.
Hendrie HC, Hall KS, Hui S, et al. Apolipoprotein E genotypes and Alzheimer's disease in a community study of elderly African Americans. Ann Neurol 1995;37:118-120.
Nalbantoglu J, Gilfix BM, Bertrand P, et al. Predictive value of apolipoprotein E genotyping in Alzheimer's disease: results of an autopsy series and an analysis of several combined studies. Ann Neurol 1994;36:889-895.
Peacock ML, Fink JK. ApoE epsilon 4 allelic association with Alzheimer's disease: independent confirmation using denaturing gradient gel electrophoresis. Neurology 1994;44:339-341.
Hendrie HC, Osuntokun BO, Hall KS, et al. Prevalence of Alzheimer's disease and dementia in two communities: Nigerian Africans and African Americans. Am J Psychiatry 1995;152:1485-1492.
Lehtimaki T, Moilanen T, Nikkari T, et al. Regional differences in apolipoprotein E polymorphism in Finland. Ann Med 1991;23:61-66.
Sobel E, Louhija J, Sulkava R, et al. Lack of association of apolipoprotein E allele epsilon 4 with late-onset Alzheimer's disease among Finnish centenarians. Neurology 1995;45:903-907.
Rebeck GW, Perls TT, West HL, Sodhi P, Lipsitz LA, Hyman BT. Reduced apolipoprotein epsilon 4 allele frequency in the oldest old Alzheimer's patients and cognitively normal individuals. Neurology 1994;44:1513-1516.
Corder EH, Saunders AM, Risch NJ, et al. Protective effect of apolipoprotein E type 2 allele for late-onset Alzheimer disease. Nature Genet 1994;7:180-184.
Talbot C, Lendon C, Craddock N, Shears S, Morris JC, Goate A. Protection against Alzheimer's disease with apoE epsilon 2 [letter]. Lancet 1994;343:1432-1433.
Benjamin R, Leake A, McArthur FK, et al. Protective effect of apoE epsilon 2 in Alzheimer's disease [letter]. Lancet 1994;344:473.
Petersen RC, Smith GE, Ivnik RJ, et al. Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals. JAMA 1995;273:1274-1278.
Tierney MC, Szalai JP, Snow WG, et al. A prospective study of the clinical utility of ApoE genotyping the prediction of outcome in patients with memory impairment. Neurology 1996;46:149-154.
Frisoni GB, Govoni S, Geroldi C. Gene dose of the epsilon 4 allele of apolipoprotein E and disease progression in sporadic lateonset Alzheimer's disease. Ann Neurol 1995;37:596-604.
Kurz A, Egensperger R, Haupt M, et al. Apolipoprotein E epsilon 4 allele, cognitive decline, and deterioration of everyday performance in Alzheimer's disease. Neurology 1996;47:440-443.
Growdon JH, Locascio JJ, Corkin S, Gomez-Isla T, Hyman BT. Apolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease. Neurology 1996;47:444-448.
Payami H, Montee KR, Kaye JA, et al. Alzheimer's disease, apolipoprotein E4, and gender. JAMA 1994;271:1316-1317.
Corder EH, Saunders AM, Strittmatter WJ, et al. The apolipoprotein E E4 allele and sex-specific risk of Alzheimer's disease. JAMA 1995;273:373-374.
Farrer LA, Cupples LA, van Duijn CM, et al. Apolipoprotein E genotype in patients with Alzheimer's disease: implications for the risk of dementia among relatives. Ann Neurol 1995;38:797-808.
Hyman BT, Gomez-Isla T, Briggs M, et al. Apolipoprotein E and cognitive change in the elderly population. Ann Neurol 1996;40:55-66.
Farrer LA, Brin MF, Elsas L, et al. Statement on use of apolipoprotein E testing for Alzheimer's disease. JAMA 1995;274:1627-1629.
National Institute on Aging/Alzheimer's Association Working Group. Apolipoprotein E genotyping in Alzheimer's disease. Lancet 1996;347:1091-1095.
McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology 1984;34:939-944.
Roses AD. Apolipoprotein E genotyping in the differential diagnosis, not prediction, of Alzheimer's disease. Ann Neurol 1995;38:6-14.
Saunders AM, Hulette C, Welsh-Bohmer KA, et al. Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease. Lancet 1996;348:90-93.
Kamboh MI, Sephernia B, Ferrell RE. Genetic studies of human apolipoproteins. VI. Common polymorphism of apolipoprotein E in blacks. Dis Markers 1989;7:49-55.
Huang DY, 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;182:55-58.
Strittmatter WJ, Weisgraber KH, Huang DY, et al. Binding of human apolipoprotein E to synthetic amyloid beta-peptide: isoform-specific effects and implications for late-onset Alzheimer's disease. Proc Natl Acad Sci USA 1993;90:8098-8102.
Miyata M, Smith JD. Apolipoprotein E allele-specific antioxidant activity and effects on cytotoxicity by oxidative insults and beta-amyloid peptides. Nature Genet 1996;14:55-61.
Small GW, Mazziotta JC, Collins MT, et al. Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer's disease. JAMA 1995;273:942-947.
Davies P, Maloney AL. Selective loss of central cholinergic neurons in Alzheimer's disease [letter]. Lancet 1976;2:1403.
Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR. Alzheimer's disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 1981;10:122-126.
Farlow M, Gracon SI, Hershey LA, et al. A controlled trial of tacrine in Alzheimer's disease. JAMA 1992;268:2523-2529.
Knapp MJ, Knopman DS, Solomon PR, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. JAMA 1994;271:985-991.
Report of the Peripheral and Central Nervous System Drugs Advisory Committee Meeting, 1989, Jul 7. Rockville, MD: Department of Health and Human Services, Public Health Service, Food and Drug Administration, 1989;227.
Schneider LS, Farlow MR. Predicting response to cholinesterase inhibitors in Alzheimer's disease: possible approaches. CNS Drugs 1995;4:144-124.
Poirier J, Delisle M-C, Quirion R, et al. Apolipoprotein E4 allele as a predictor of cholinergic deficits and treatment outcome in Alzheimer's disease. Proc Natl Acad Sci USA 1995;92:12260-12264.
Farlow MR, Lahiri D, Hui S, Davignon J. Apolipoprotein E genotype predicts response to tacrine in Alzheimer's disease [abstract]. Neurology 1996;46(suppl 2):A217.

Information & Authors


Published In

Volume 48Number 5_suppl_6May 1997
Pages: 30S-34S

Publication History

Published online: May 1, 1997
Published in print: May 1997


Request permissions for this article.


Affiliations & Disclosures

From the Department of Neurology, Indiana University School of Medicine, Indianapolis, IN.
Address correspondence and reprint requests to Dr. Martin R. Farlow, Indiana University Medical Center, Department of Neurology, 541 Clinical Drive, Suite 583, Indianapolis, IN 46202-5111.

Metrics & Citations



Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
  1. Neuropsychiatric Inventory–Questionnaire Assessed Nighttime Behaviors in Cognitively Asymptomatic Patients with Pathologically Confirmed Alzheimer’s Disease Predict More Rapid Cognitive Deterioration, Journal of Alzheimer's Disease, 86, 3, (1137-1147), (2022).
  2. Abnormal Sleep Behaviours Across the Spectrum of Alzheimer’s Disease Severity: Influence of APOE Genotypes and Lewy Bodies, Current Alzheimer Research, 16, 3, (243-250), (2019).
  3. When it runs in the family: putting susceptibility genes in perspective, Public Understanding of Science, 15, 3, (277-300), (2016).
  4. Amnestic mild cognitive impairment, The Behavioral Neurology of Dementia, (217-231), (2016).
  5. Mapping the Effect of the Apolipoprotein E Genotype on 4-Year Atrophy Rates in an Alzheimer Disease–related Brain Network, Radiology, 271, 1, (211-219), (2014).
  6. Assessment of Suspected Dementia, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, 28, S1, (S28-S41), (2014).
  7. Dissecting the Gene Dose-Effects of the APOE ε4 and ε2 Alleles on Hippocampal Volumes in Aging and Alzheimer’s Disease, PLoS ONE, 8, 2, (e54483), (2013).
  8. Genetics of Alzheimer Disease, Emery and Rimoin's Principles and Practice of Medical Genetics, (1-20), (2013).
  9. Isoform‐specific effects of apolipoprotein E on cognitive performance in targeted‐replacement mice overexpressing human APP, Genes, Brain and Behavior, 9, 2, (182-192), (2010).
  10. Molecular genetics of Alzheimer's disease and other adult-onset dementias, Genes and Common Diseases, (439-453), (2009).
  11. See more

View Options

Get Access

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

Purchase this article to get full access to it.

Purchase Access, $39 for 24hr of access

View options

Full Text

View Full Text

Full Text HTML

View Full Text HTML







Share article link