Prevalence of Apolipoprotein E4 Genotype and Homozygotes (APOE e4/4) among Patients Diagnosed with Alzheimer’s Disease: A Systematic Review and Meta-AnalysisWard A.a · Crean S.a · Mercaldi C.J.b · Collins J.M.a · Boyd D.a · Cook M.N.c · Arrighi H.M.d
aCenter for Epidemiology and Database Analytics, United BioSource Corporation, Lexington, Mass., bCenter for Epidemiology and Database Analytics, United BioSource Corporation, Bethesda, Md., cPfizer Inc., Collegeville, Pa., and dJANSSEN Alzheimer Immunotherapy Research and Development, LLC, South San Francisco, Calif., USA
Alex Ward, PhD, MRPharmS
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Background: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer’s disease (AD) by geographic region and country. Methods: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. Results: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5–51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4–10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9–66.7), e4/4 prevalence: 14.1% (95% CI: 12.2–16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. Conclusions: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.
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Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, Copeland JR, Dartigues JF, Jagger C, Martinez-Lage J, Soininen H, Hofman A: Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54:S4–S9.
- Davidson Y, Gibbons L, Pritchard A, Hardicre J, Wren J, Stopford C, Julien C, Thompson J, Payton A, Pickering-Brown SM, Pendleton N, Horan MA, Burns A, Purandare N, Lendon CL, Neary D, Snowden JS, Mann DM: Apolipoprotein E epsilon4 allele frequency and age at onset of Alzheimer’s disease. Dement Geriatr Cogn Disord 2007;23:60–66.
- Roses AD: On the discovery of the genetic association of apolipoprotein E genotypes and common late-onset Alzheimer disease. J Alzheimers Dis 2006;9:361–366.
- 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;278:1349–1356.
- Bettens K, Sleegers K, Van Broeckhoven C: Current status on Alzheimer disease molecular genetics: from past, to present, to future. Hum Mol Genet 2010;19:R4–R11.
- Corbo RM, Scacchi R: Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? Ann Hum Genet 1999;63:301–310.
- Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Stroehla BC: Apolipoprotein E polymorphism and cardiovascular disease: a huge review. Am J Epidemiol 2002;155:487–495.
- Singh PP, Singh M, Mastana SS: APOE distribution in world populations with new data from India and the UK. Ann Hum Biol 2006;33:279–308.
- DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.
Hedges L, Olkin I: Statistical Methods for Meta-Analysis. Orlando, Academic Press, 1985.
- Higgins JP, Thompson SG, Deeks JJ, Altman DG: Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.
- Berkey CS, Hoaglin DC, Mosteller F, Colditz GA: A random-effects regression model for meta-analysis. Stat Med 1995;14:395–411.
- Tsuang D, Kukull W, Sheppard L, Barnhart RL, Peskind E, Edland SD, Schellenberg G, Raskind M, Larson EB: Impact of sample selection on APOE epsilon 4 allele frequency: a comparison of two Alzheimer’s disease samples. J Am Geriatr Soc 1996;44:704–707.
- Crean S, Ward A, Mercaldi CJ, Collins JM, Cook MN, Baker NL, Arrighi HM: Apolipoprotein E e4 prevalence in Alzheimer’s disease patients varies across global populations: a systematic literature review and meta-analysis. Dement Geriatr Cogn Disord, 2011;31:20–30.
- Bowirrat A, Oscar-Berman M, Logroscino G: Association of depression with Alzheimer’s disease and vascular dementia in an elderly Arab population of Wadi-Ara, Israel. Int J Geriatr Psychiatry 2006;21:246–251.
- Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O’Brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P: Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734–746.
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