Skip to main content
AAN.com
Articles
February 8, 2000

APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives

February 8, 2000 issue
54 (3) 593

Abstract

Objective: To examine the independent effects of the APOE genotype (APOE) and concordance for AD in twin pairs on the occurrence of AD in first-degree relatives.
Background: Studies of twins have been undertaken to investigate the influence of genes in a variety of conditions, including AD. A previous study, performed before reports linking APOE to AD, demonstrated an increase in AD among first-degree relatives of twins concordant for AD compared with relatives of discordant twins.
Methods: In a sample of 94 twin pairs the authors examined the association between concordance for AD within the twin pair and family history of AD among first-degree relatives of twins. They then examined the extent to which the presence of the APOE ε4 allele in the twin pair explains the association between concordance for AD within the twin pair and family history of AD.
Results: Concordance among twins was associated with increased risk of AD among relatives (logrank test, χ2 = 12.558; p = 0.0004), and the presence of at least one APOE ε4 allele in each member of the twin pair is also associated with increased risk of AD among family members (logrank test, χ2 = 7.712; p = 0.0055).
Conclusions: APOE genotype explains much but not all of the association between concordance among twins and increased familial risk of AD.

Get full access to this article

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

References

1.
Saunders AM, Strittmatter WJ, Schmechel D, et al. Association of apolipoprotein E allele E4 with late-onset familial and sporadic Alzheimer’s disease. Neurology 1993;43:1467–1472.
2.
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.
3.
Karlinsky H, Berg JM, Lennox A, et al. Monozygotic twins concordant for late-onset probable Alzheimer disease with suspected Alzheimer disease in four sibs. Am J Med Genet 1992;44:591–597.
4.
Rapoport SI, Pettigrew KD, Schapiro MB. Discordance and concordance of dementia of the Alzheimer type (DAT) in monozygotic twins indicate heritable and sporadic forms of Alzheimer’s disease. Neurology 1991;41:1549–1553.
5.
Breitner JCS, Welsh KA, Gau BA, et al. Alzheimer’s disease in the National Academy of Sciences–National Research Council Registry of aging twin veterans. III. Detection of patients, longitudinal results, and observations on twin concordance. Arch Neurol 1995;52:763–771.
6.
Brandt JM, Spencer M, Folstein M. The telephone interview for cognitive status. Neuropsychiatry Neuropsychol Behav Neurol 1988;1:111–117.
7.
Welsh KA, Breitner JCS, Magruder–Habib KM. Detection of dementia in the elderly using telephone screening of cognitive status. Neuropsychiatry Neuropsychol Behav Neurol 1993;6:103–110.
8.
Silverman JM, Breitner JCS, Mohs RC, Davis KL. Reliability of the family history method in genetic studies of Alzheimer’s disease and related dementias. Am J Psychiatry 1986;143:1279–1282.
9.
Gallo JJ, Breitner JCS. Alzheimer’s disease in the N.A.S.- N.R.C. Registry of aging twin veterans. IV. Performance characteristics of a two-stage telephone screening procedure for Alzheimer’s dementia. Psychol Med 1995;25:1211–1219.
10.
Ellis RJ, Jan K, Kawas C, et al. Diagnostic validity of the Dementia Questionnaire for Alzheimer disease. Arch Neurol 1998;55:360–365.
11.
Steffens DC, Welsh KA, Burke J, et al. Diagnosis of Alzheimer’s disease in epidemiologic studies by staged review of clinical data. Neuropsychiatry Neuropsychol Behav Neurol 1996;9:107–113.
12.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. 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.
13.
Mirra SS, Heyman A, McKeel D, et al. The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 1991;41:479–486.
14.
Torgersen S. The determination of twin zygosity by means of a mailed questionnaire. Acta Genet Med Gemellol (Roma) 1979;28:225–236.
15.
Cederlof R, Friberg L, Jonsson E, Kaij L. Studies on similarity diagnosis in twins with the aid of mailed questionnaires. Acta Genet (Basel) 1961;11:338–362.
16.
Wenham PR, Price WH, Blundell G. Apolipoprotein E genotyping by one-stage PCR. Lancet 1991;337:1158–1159.
17.
Hixson JE, Vernier DR. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with Hha I. J Lipid Res 1990;31:545–548.
18.
Payami H, Grimslid H, Oken B, et al. A prospective study of cognitive health in the elderly (Oregon Brain Aging Study): effects of family history and apolipoprotein E genotype. Am J Hum Genet 1997;60:948–956.
19.
Martinez M, Campion D, Brice A, et al. Apolipoprotein E epsilon 4 allele and familial aggregation of Alzheimer disease. Arch Neurol 1998;55:810–816.
20.
Duara R, Barker WW, Lopez–Alberola R, et al. Alzheimer’s disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset. Neurology 1996;46:1575–1579.
21.
Reed T, Carmelli D, Swan GE, et al. Lower cognitive performance in normal older adult male twins carrying the apolipoprotein E epsilon 4 allele. Arch Neurol 1994;1:1189–1192.
22.
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.
23.
Mayeux R, Saunders AM, Shea S, et al. Utility of the apolipoprotein E genotype in the diagnosis of Alzheimer’s disease. Alzheimer’s Disease Centers Consortium on Apolipoprotein E and Alzheimer’s Disease. N Engl J Med 1998;338:506–511.
24.
Pericak–Vance MA, Bass MP, Yamaoka LH, et al. Complete genomic screen in late-onset familial Alzheimer disease. Evidence for a new locus on chromosome 12. JAMA 1997;278:1237–1241.
25.
Blacker D, Wilcox MA, Laird NM, et al. Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat Genet 1998;19:357–360.

Information & Authors

Information

Published In

Neurology®
Volume 54Number 3February 8, 2000
Pages: 593
PubMed: 10680788

Publication History

Received: March 26, 1999
Accepted: September 25, 1999
Published online: February 8, 2000
Published in print: February 8, 2000

Permissions

Request permissions for this article.

Authors

Affiliations & Disclosures

D.C. Steffens, MD
From the Department of Psychiatry and Behavioral Sciences (Drs. SteffensPlassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.
B.L. Plassman, PhD
From the Department of Psychiatry and Behavioral Sciences (Drs. SteffensPlassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.
M.J. Helms, BS
From the Department of Psychiatry and Behavioral Sciences (Drs. SteffensPlassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.
K.A. Welsh–Bohmer, PhD
From the Department of Psychiatry and Behavioral Sciences (Drs. SteffensPlassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.
T.T. Newman, BS
From the Department of Psychiatry and Behavioral Sciences (Drs. SteffensPlassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.
J.C. S. Breitner, MD, MPH
From the Department of Psychiatry and Behavioral Sciences (Drs. SteffensPlassman, Welsh–Bohmer, and Breitner, and M. Helms and T. Newman) and the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Dr. Welsh–Bohmer), Duke University Medical Center, Durham, NC; and the School of Public Health, Division of Mental Hygiene, Johns Hopkins University (Dr. Breitner), Baltimore, MD.

Notes

Address correspondence and reprint requests to Dr. David C. Steffens, Duke University Medical Center, Box 3903, Durham, NC 27710.

Metrics & Citations

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. Genetics of Brain Aging – Twin Aging☆, Reference Module in Biomedical Sciences, (2015).https://doi.org/10.1016/B978-0-12-801238-3.04608-0
    Crossref
  2. Neuropathologic Assessment of Dementia Markers in Identical and Fraternal Twins, Brain Pathology, 24, 4, (317-333), (2014).https://doi.org/10.1111/bpa.12127
    Crossref
  3. Dementia: Genes, Environments, Interactions, Behavior Genetics of Cognition Across the Lifespan, (201-231), (2013).https://doi.org/10.1007/978-1-4614-7447-0_7
    Crossref
  4. What monozygotic twins discordant for phenotype illustrate about mechanisms influencing genetic forms of neurodegeneration, Clinical Genetics, 81, 4, (325-333), (2011).https://doi.org/10.1111/j.1399-0004.2011.01795.x
    Crossref
  5. Genetic Risk Factors for Dementia, The Handbook of Alzheimer's Disease and Other Dementias, (195-234), (2011).https://doi.org/10.1002/9781444344110.ch6
    Crossref
  6. Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease, Neurobiology of Aging, 29, 8, (1190-1198), (2008).https://doi.org/10.1016/j.neurobiolaging.2007.02.017
    Crossref
  7. Genetics of Alzheimer's Disease: A Centennial Review, Neurologic Clinics, 25, 3, (611-667), (2007).https://doi.org/10.1016/j.ncl.2007.03.009
    Crossref
  8. Genomic regulation after CD40 stimulation in microglia: Relevance to Alzheimer's disease, Molecular Brain Research, 140, 1-2, (73-85), (2005).https://doi.org/10.1016/j.molbrainres.2005.07.014
    Crossref
Loading...

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 access the full text.

Purchase Access, $39 for 24hr of access

View options

Full Text HTML

View Full Text HTML

Media

Figures

Other

Tables

Share

Share

Share article link

Share