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Genetic and environmental epidemiology of Alzheimer’s disease in arabs residing in Israel

  • Genetics And Prevention
  • Published:
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Abstract

We have found an unusually high prevalence of Alzheimer’s disease (AD) in Wadi Ara, an inbred Arab community in northern Israel. Allele frequencies of 4.5% and 3.5% were found for the apolipoprotein E e4 allele among AD cases and nondemented controls, respectively, showing that other genetic or environmental influences must be responsible. Family studies revealed that more than one-third of the AD cases are members of one hamula (tribal group) within Wadi Ara. We hypothesize that the high risk of AD in this genetic isolate may be attributable to a founder effect enhanced by consanguinity. It is also possible that smoking or high fat diet are responsible. To map chromosomal loci contributing to AD susceptibility, we conducted a genome scan from specific hamulas and followed candidate regions found to be linked to disease. Markers from 18 chromosomal regions showed significant allelic association with AD. Smoking was very common in men but was not linked to the presence of AD in Wadi Ara, The unique characteristics of this community, together with the large amount of human genome data, should allow for the identification of AD genes in candidate regions.

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References

  • Abraham R., Myers A., Wavrant-DeVrieze F., Hamshere M. L., Thomas H. V., Marshall H., Compton D., et al. (2001) Substantial linkage disequilibrium across the insulindegrading enzyme locus but no association with lateonset Alzheimer’s disease. Hum. Genet. 109, 646–652.

    Article  PubMed  CAS  Google Scholar 

  • Baldwin C. T., Weiss S., Farrer L. A., et al. (1995) Linkage of congential, recessive deafness (DFNB4) to human chromosome 7q31 in the Middle Eastern Druze population and evidence for genetic heterogeneity. Hum. Mol. Genet. 4, 1637–1642.

    Article  PubMed  CAS  Google Scholar 

  • Bertram L., Blacker D., Mullin K., et al. (2000) Evidence for genetic linkage of Alzheimer’s disease to chromosome 10q. Science 290, 2302–2303.

    Article  PubMed  CAS  Google Scholar 

  • Blacker D., Wilcox M. A., Laird N. M., et al. (1998) Alpha-2 macroglobulin is genetically associated with Alzheimer disease. Nat. Genet. 19, 357–360.

    Article  PubMed  CAS  Google Scholar 

  • Bonné-Tamir B., DeStefano A. L., Briggs C. E., et al. (1996) Linkage of congenital recessive deafness (DFNB10) to chromosome 21q22.3. Am. J. Hum. Genet. 58, 1254–1259.

    Google Scholar 

  • Bowirrat A., Friedland R. P., Chapman J., and Korczyn A. D. (2000) The very high prevalence of Alzheimer’s disease in an Arab population is not explained by APOE e4 allele frequency. Neurology 55, 731.

    PubMed  CAS  Google Scholar 

  • Bowirrat A., Treves T. A., Friedland R. P., and Korczyn A. D. (2001) Prevalence of Alzheimer’s type dementia in an elderly Arab population. Eur. Neurol. 8, 1–5.

    Google Scholar 

  • Brenner D. E., Kukull W. A., Van Belle G., et al. (1993) Relationship between cigarette smoking and Alzheimer’s disease in a population-based case-control study. Neurology 43, 293–300.

    PubMed  CAS  Google Scholar 

  • Corder E. H., Saunders A. M., Strittmatter W.J., et al. (1993) Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late-onset families. Science 261, 921–923.

    Article  PubMed  CAS  Google Scholar 

  • Debanne S. M., Rowland D. Y., Riedel T. M., et al. (2000) Association of Alzheimer’s disease and smoking: the case for sibling controls. J. Am. Geriatr. Soc. 48, 800–806.

    PubMed  CAS  Google Scholar 

  • Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (1994) American Psychiatric Association, Washington, D.C.

  • Doll R., Peto R., Boreham J., et al. (2000) Smoking and dementia in male British doctors: prospective study. Br. Med. J. 320, 1097–1102.

    Article  CAS  Google Scholar 

  • Doll R., Peto R., Wheatly K., et al. (1994) Mortality in relation to smoking: 40 years’ observations on male British doctors. Br. Med. J. 309, 901–911.

    CAS  Google Scholar 

  • Ertekin-Taner N., Graff-Radford N., Younkin L. H., et al. (2000) Linkage of plasma A42 to a quantitative locus on chromosome 10 in late-onset Alzheimer’s disease pedigrees. Science 290, 2303–2304.

    Article  PubMed  CAS  Google Scholar 

  • Farrer L. A., Cupples L. A., Haines J. L., et al. (1997) Effects of age, gender and ethnicity on the association of apolipoprotein E genotype and Alzheimer disease. JAMA 278, 1349–1356.

    Article  PubMed  CAS  Google Scholar 

  • Farrer L. A., Bowirrat A., Friedland, R. P., et al. (2003) Identification of multiple loci for Alzheimer’s disease in a consanguineous Israeli-Arab community. Hum. Mol. Genet. 12, 415–422.

    Article  PubMed  CAS  Google Scholar 

  • Ford A. B., Mefrouche Z., Friedland R., et al. (1996) Smoking and cognitive impairment: A population-based study. J. Am. Geriatr. Soc. 44, 905–909.

    Google Scholar 

  • Frydman M., Bonné-Tamir B., Farrer L. A., Conneally P. M., Magazanik A., Ashbel S., and Goldwitch Z. (1985) Assignment of the gene for Wilson disease to chromosome 13: linkage to the esterase-D locus. Proc. Natl. Acad. Sci. U.S.A. 82, 1819–1821.

    Article  PubMed  CAS  Google Scholar 

  • Graves A. B., Van Duijin C. M., Chandra V., et al. (1991) Alcohol and tobacco consumption as risk factors for Alzheimer’s disease: a collaborativere-analysis of case-control studies. Int. J. Epidemiol. 20, S48-S57.

    PubMed  Google Scholar 

  • Hendrie H. C., Ogunniyi A., Hall K. S., et al. (2001) Incidence of dementia and Alzheimer disease in 2 communities: Yoruba residing in Ibadan, Nigeria, and African Americans residing in Indianapolis, Indiana. JAMA 285, 739–747.

    Article  PubMed  CAS  Google Scholar 

  • Jarvik G. P., Larson E. B., Goddard K., Kukull W. A., Schellenberg G. D., and Wijsman E. M. (1996) Influence of apolipoprotein E genotype on the transmission of Alzheimer disease in a community-based sample. Am. J. Hum. Genet. 58, 191–200.

    Google Scholar 

  • Kang D. E., Saitoh T., Chen X., Xia Y., Masliah E., Hansen L. A., et al. (1997) Genetic association of the low-density lipoprotein receptor-related protein gene (LRP), an apolipoprotein E receptor, with late-onset Alzheimer’s disease. Neurology 49, 5661.

    Google Scholar 

  • Koelega H. S. (1993) Stimulant drugs and vigilance performance: a review. Psychopharmacology 111, 1–16.

    Article  PubMed  CAS  Google Scholar 

  • Korovaitseva G. I., Premkumar S., Grigorenko A., et al. (1999) Alpha-2 macroglobulin gene in early- and late-onset Alzheimer disease. Neurosci. Lett. 271, 129–131.

    Article  PubMed  CAS  Google Scholar 

  • Lee P.N. (1994) Smoking and Alzheimer’s disease: a review of the epidemiological evidence. Neuroepidemiology 13, 131–144.

    PubMed  Google Scholar 

  • Levin E. D., Conners C. K., Silvia D., et al. (1998) Transdermal nicotine effects on attention. Psychopharmacology 140, 135–141.

    Article  PubMed  CAS  Google Scholar 

  • Mayeux R., Lee J. H., Romas S. N., et al. (2002) Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics. Am. J. Hum. Genet. 70, 237–243.

    Article  PubMed  CAS  Google Scholar 

  • Merchant C., Tang M.-X., Albert S., et al. (1999) The influence of smoking on the risk of Alzheimer’s disease. Neurology 52, 1408–1412.

    PubMed  CAS  Google Scholar 

  • Myers A., Holmans P., Marshall H., et al. (2000) Susceptibility locus for Alzheimer’s disease on chromosome 10. Science 290, 2304–2305.

    Article  PubMed  CAS  Google Scholar 

  • Myers A. J. and Goate A. M. (2001) The genetics of lateonset Alzheimer’s disease. Curr. Opin. Neurol. 14, 433–440.

    Article  PubMed  CAS  Google Scholar 

  • Osuntokun B. O., Sahota A., Ogunniyi A. O., et al. (1995) Lack of an association between apolipoprotein E 4 and Alzheimer’s disease in elderly Nigerians. Ann. Neurol. 38, 463–465.

    Article  PubMed  CAS  Google Scholar 

  • Ott A., Slooter A. J. C., Hofman A., Van Harskamp J. C. M., et al. (1998) Smoking and risk of dementia and Alzheimer’s disease in a population-based cohort study: The Rotterdam Study. Lancet 351, 1840–1843.

    Article  PubMed  CAS  Google Scholar 

  • Pericak-Vance M. A., Bass M. P., Yamaoka L. H., et al. (1997) Complete genomic screen in late-onset familial Alzheimer disease: Evidence for a new locus on chromosome 12. JAMA 278, 1237–1241.

    Article  PubMed  CAS  Google Scholar 

  • Pericak-Vance M. A., Grubber J., Bailey L. R., et al. (2000) Identification of novel genes in late-onset Alzheimer’s disease. Exp. Gerontol. 35, 1343–1352.

    Article  PubMed  CAS  Google Scholar 

  • Pericak-Vance M. A., Johnson C. C., Rimmler J. B., Saunders A. M., Robinson L. C., D’Hondt E. G., et al. (1996) Alzheimer’s disease and apolipoprotein E-4 allele in an Amish population. Ann. Neurol. 39, 700–704.

    Article  Google Scholar 

  • Perry E. K., Gibson P. H., Blessed G., et al. (1977) Neurotransmitter enzyme abnormalities in senile dementia. J. Neurol. Sci. 34, 247–265.

    Article  PubMed  CAS  Google Scholar 

  • Rao V. S., Cupples L. A., van Duijn C. M., et al. (1996) Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4. Am. J. Hum. Genet. 59, 664–675.

    Google Scholar 

  • Rao V. S., van Duijn C. M., Connor-Lacke L., Growdon J. H., and Farrer L. A. (1994) Multiple etiologies for Alzheimer disease revealed by segregation analysis. Am. J. Hum. Genet. 55, 991–1000.

    PubMed  CAS  Google Scholar 

  • Riggs J. E. (1993) Smoking and Alzheimer’s disease: protective effect or differential survival bias? Lancet 342, 792–794.

    Article  Google Scholar 

  • Rocca W. A., Hofman A., Brayne C., et al. (1991) Frequency and distribution of Alzheimer’s disease in Europe: a collaborative study of 1980–1990 prevalence findings. Ann. Neurol. 30, 381–390.

    Article  PubMed  CAS  Google Scholar 

  • Rogaeva E., Premkumar S., Song Y., et al. (1998) Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. JAMA 280, 614–618.

    Article  PubMed  CAS  Google Scholar 

  • Rogaeva E. A., Premkumar S., Grubber J., et al. (1999) A comprehensive examination of an α-2-macroglobulin insertion-deletion polymorphism in Alzheimer disease. Nat. Genet. 2, 19–20.

    Google Scholar 

  • Schellenberg G. D., D’Souza I., and Poorkaj P. (2000) The genetics of Alzheimer’s disease. Curr. Psychiatry Rep. 2, 158–164.

    Article  PubMed  CAS  Google Scholar 

  • Scott W. K., Yamaoka L. H., Bass M. L., et al. (1998) No genetic association between the LRP receptor and sporadic or late-onset familial Alzheimer disease. Neurogenetics 1, 179–183.

    Article  PubMed  CAS  Google Scholar 

  • Shimohama S., Taniguchi T., Fujiwara M., et al. (1986) Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer type dementia. J. Neurochem. 46, 288–293.

    Article  PubMed  CAS  Google Scholar 

  • Terzano D. L., Beach T. G., Lukas R. J., et al. (1998) Immunohistochemical localization of nicotinic β2 and β4 receptor subunits in normal human brain and individuals with Lewy body and Alzheimer’s disease: preliminary observation. Neurosci. Lett. 256, 151–154.

    Article  Google Scholar 

  • Utsugisawa K., Nagane Y., Tongi H., et al. (1999) Changes with aging and ischemia in nicotinic acetylcholine receptor subunit α7 mRNA expression in postmortem human frontal cortex and putamen. Neurosci. 270, 145–148.

    CAS  Google Scholar 

  • Van Duijn C. M., Farrer L. A., Cupples L. A., and Hofman A. (1993) Genetic transmission for Alzheimer disease among patients identified in a Dutch population based survey. J. Med. Genet. 30, 640–646.

    Article  PubMed  Google Scholar 

  • Van Duijn C. N., Clayton D. G., Chandra V., et al. (1994) Interaction between genetic and environmental risk factors for Alzheimer’s disease: a reanalysis of case-control studies. Genet. Epidemiol. 11, 539–551.

    Article  PubMed  Google Scholar 

  • Whitehouse P. J., Martino A. M., Wagster M. V., et al. (1998) Reductions in (3H) nicotinic acetylcholine binding in Alzheimer’s disease and Parkinson’s disease: an autoradiographic study. Neurology 39, 720–723.

    Google Scholar 

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Correspondence to Robert P. Friedland.

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Farrer, L.A., Friedland, R.P., Bowirrat, A. et al. Genetic and environmental epidemiology of Alzheimer’s disease in arabs residing in Israel. J Mol Neurosci 20, 207–212 (2003). https://doi.org/10.1385/JMN:20:3:207

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  • DOI: https://doi.org/10.1385/JMN:20:3:207

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