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Association of Decreased Paternal Age and Late-Onset Alzheimer's Disease: An Example of Genetic Imprinting?

Association of Decreased Paternal Age and Late-Onset Alzheimer's Disease: An Example of Genetic... Abstract • Several studies have identified advanced maternal age as a risk factor for Alzheimer's disease. This study evaluated maternal and paternal age at birth of 237 patients with Alzheimer's disease, each of whom was matched to five control subjects based on sex, year of birth, survival age, and location of residence. It was found that decreased paternal age substantially increased the susceptibility to the common form of Alzheimer's disease that occurs after the age of 67 years, whereas advanced maternal age had a negligible effect on risk of Alzheimer's disease. The higher incidence of late-onset Alzheimer's disease among persons born to younger fathers is consistent with a genetic imprinting mechanism involving DNA methylation. The proposed model postulates a role for environmental agents in the pathogenesis of Alzheimer's disease and accounts for families that show an aggregation of cases but no apparent pattern of inheritance. References 1. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer's disease in a community population of older persons . JAMA . 1989;262:2551-2556.Crossref 2. Goudsmit J, Morrow CH, Asher DM, et al. Evidence for and against transmissibility of Alzheimer's disease . Neurology . 1980;30:945-950.Crossref 3. Mortimer JA, French LR, Hutton JT, Schuman LM. Head injury as a risk factor for Alzheimer's disease . Neurology . 1985;35:264-267.Crossref 4. Crapper McLachlan DR. Aluminum and Alzheimer's disease . Neurobiol Aging . 1986;7:525-532.Crossref 5. Birchall JD, Chappall JS. Aluminum, chemical physiology, Alzheimer's disease . Lancet . 1988;2:1008-1010.Crossref 6. Manuelidis EE, de Figueredo JM, Kim JH, Fritch WW, Manuelidis L. Transmission studies from blood of Alzheimer disease patients and healthy relatives . Proc Natl Acad Sci U S A . 1988;85:4898-4901.Crossref 7. Martyn CN, Barker DJP, Osmond C, Harris EC, Edwardson JA, Jacey RF. Geographical relation between Alzheimer's disease and aluminum in the drinking water . Lancet . 1989;1:59-62. 8. Haberland G. Alzheimer's disease in Down's syndrome . Acta Neurol Belg . 1969;69:369-380. 9. Heston LL. Alzheimer's disease, trisomy 21, and myeloproliferative disorders: associations suggesting a genetic diathesis . Science . 1977;196:322-323.Crossref 10. Ellis WG, McCulloch JR, Corley CL. Presenile dementia in Down's syndrome: ultrastructural identity with Alzheimer's disease . Neurology . 1974;24:101-106.Crossref 11. Wisniewski K, Howe J, Williams DG, Wisniewski HM. Precocious aging and dementia in patients with Down's syndrome . Biol Psychiatry . 1978;13:619-627. 12. Mann DMA. The pathological association between Down syndrome and Alzheimer disease . Mech Ageing Dev . 1988;43:99-136.Crossref 13. Penrose LS. The relative effects of paternal and maternal age in mongolism . J Genet . 1933;27:219-224.Crossref 14. Cohen D, Eisdorfer C, Leverenz J. Alzheimer's disease and maternal age . J Am Geriatr Soc . 1982;30:656-659. 15. Whalley LJ, Carothers AD, Collyer S, De Mey R, Frackiewicz A. A study of familial factors in Alzheimer's disease . Br J Psychiatry . 1982;140:249-256.Crossref 16. Amaducci LA, Fratiglioni L, Rocca WA, et al. Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population . Neurology . 1986;36:922-931.Crossref 17. Urakami K, Adachi Y, Takahashi K. A community-based study of parental age at the birth of patients with dementia of the Alzheimer type . Arch Neurol . 1989;46:38-39.Crossref 18. Corkin S, Growdon JH, Rasmussen SL. Parental age as a risk factor in Alzheimer's disease . Ann Neurol . 1983;13:674-676.Crossref 19. Heyman A, Wilkinson WE, Hurwitz BJ, et al. Alzheimer's disease: genetic aspects and associated clinical disorders . Ann Neurol . 1983;14:507-515.Crossref 20. English D, Cohen D. A case-control study of maternal age in Alzheimer's disease . J Am Geriatr Soc . 1985;33:167-169. 21. White JA, McGue M, Heston LL. Fertility and parental age in Alzheimer's disease . J Gerontol . 1986;41:40-43.Crossref 22. Khachaturian ZS. Diagnosis of Alzheimer's disease . Arch Neurol . 1985;42:1097-1105.Crossref 23. McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan D. 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;34:939-945.Crossref 24. Farrer LA, O'Sullivan DM, Cupples LA, Growdon JH, Myers RH. Assessment of genetic risk for Alzheimer's disease among first-degree relatives . Ann Neurol . 1989;25:485-493.Crossref 25. Dawber TR, Meadors GF, Moore FE. Epidemiological approaches to heart disease: the Framingham Study . Am J Public Health . 1951;41:279-286.Crossref 26. Schildkraut JM, Myers RH, Cupples LA, Kiely DJ, Kannel WB. Coronary risk associated with age and sex of parental heart disease in the Framingham study . Am J Cardiol . 1989;64:555-559.Crossref 27. Gail M, Williams R, Byar DP, Brown C. How many controls? J Chronic Dis . 1976;29:723-731.Crossref 28. Sokal RR, Rohlf RJ. Biometry . 2nd ed. New York, NY: WH Freeman & Co; 1981. 29. Chui HC, Teng EL, Henderson VW, Moy AC. Clinical subtypes of dementia of the Alzheimer type . Neurology . 1985;35:1544-1550.Crossref 30. Mayeux R, Stern Y, Spanton S. Heterogeneity in dementia of the Alzheimer type: evidence of subgroups . Neurology . 1985;35:453-461.Crossref 31. Farrer LA, Myers RH, Cupples LA, et al. Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity . Neurology . 1990;40:395-403.Crossref 32. St George-Hyslop PH, Myers RH, Haines JL, et al. Familial Alzheimer's disease: progress and problems . Neurobiol Aging . 1989;10:417-425.Crossref 33. Breslow NE, Day NE, Halvorsen KT, Prentice RL, Sabai C. Estimation of multiple relative risk functions in matched case-control studies . Am J Epidemiol . 1978;108:299-307. 34. SAS User's Guide: Statistics . Cary, NC: SAS Inc; 1986. 35. White L, Wolf PA, Farmer M, et al. Neuropsychologic test performance in later life: a cross-sectional study of the Framingham Heart Study cohort . Am J Epidemiol . 1983;118:444. Abstract. 36. Hassold TJ, Jacobs PA. Trisomy in man . Annu Rev Genet . 1984;18:69-67.Crossref 37. Buckton KE, Whalley LJ, Lee M, Christie JE. Chromosome changes in Alzheimer's presenile dementia . J Med Genet . 1983;20:46-51.Crossref 38. St George-Hyslop P, Tanzi RE, Polinsky RJ, et al. The genetic defect causing familial Alzheimer's disease maps on chromosome 21 . Science . 1987;235:885-890.Crossref 39. Goate AM, Haynes AR, Owen MJ, et al. Predisposing locus for Alzheimer's disease on chromosome 21 . Lancet . 1989;1:352-355.Crossref 40. Van Broeckhoven C, Van Hul W, Backhovens H, et al. The familial Alzheimer's disease gene is located close to the centromere on chromosome 21 . Am J Hum Genet . 1988;43( (suppl) ):A205. Abstract. 41. St George-Hyslop PH, Haines JL, Farrer LA, et al. Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder . Nature . 1990;347:194-197.Crossref 42. Delabar JM, Goldgaber D, Lamour Y, et al. β Amyloid gene duplication in Alzheimer's disease and karyotypically normal Down syndrome . Science . 1987;235:1390-1392.Crossref 43. Schweber M, Tuson C, Shiloh R, Ben-Neriah Z. Triplication of chromosome 21 material in Alzheimer's disease . Neurology . 1987;37( (suppl 1) ):222. Abstract. 44. St George-Hyslop PH, Tanzi RE, Polinsky RJ, et al. Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease . Science . 1987;238:664-666.Crossref 45. Tanzi RE, Bird ED, Latt SA, Neve RL. The amyloid β protein gene is not duplicated in brains from patients with Alzheimer's disease . Science . 1987;238:666-669.Crossref 46. Berman M, Lee G, Selkoe DJ. Gene dosage of the amyloid β precursor protein in Alzheimer's disease . Science . 1987;238:669-671.Crossref 47. Hall JG. Genomic imprinting: review and relevance to human diseases . Am J Hum Genet . 1990;46:857-873. 48. Hadchouel M, Farza H, Simon D, Tiollias P, Poucel C. Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation . Nature . 1987;329:454-456.Crossref 49. Monk M, Boubelik M, Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse development . Development . 1987;99:371-382. 50. Reik W, Collick A, Norris ML, Barton SC, Surani MAH. Genomic imprinting determines methylation of parental alleles in transgenic mice . Nature . 1987;328:248-251.Crossref 51. Sapienza C, Peterson AC, Rossant J, Balling R. Degree of methylation of transgenes is dependent on gamete of origin . Nature . 1987;328:251-254.Crossref 52. Swain JL, Stewart TA, Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting . Cell . 1987;50:719-727.Crossref 53. Holliday R. A different kind of inheritance . Sci Am . (June) 1989:60-73. 54. Vogel F, Rathenberg R. Spontaneous mutation in man . Adv Hum Genet . 1975;5:223-318. 55. Berg L. Does Alzheimer's disease represent an exaggeration of normal aging? Arch Neurol . 1985;42:737-739.Crossref 56. Mann DMA, Yates PO, Marcyniuk B. Alzheimer's presenile dementia, senile dementia of the Alzheimer type and Down's syndrome in middle age form an age related continuum of pathological changes . Neuropathol Appl Neurobiol . 1985;10:185-207.Crossref 57. Brayne C, Calloway P. Normal ageing, impaired cognitive function, and senile dementia of the Alzheimer's type: a continuum? Lancet . 1988;1:1265-1267.Crossref 58. Farrer LA. Genetic neurodegenerative disease models for human aging . In: Rothstein M, ed. Review of Biological Research in Aging . New York, NY: Alan R Liss Inc; 1987;3:163-189. 59. Ridley RM, Frith CD, Crow TJ, Conneally PM. Anticipation in Huntington's disease is inherited through the male line but may originate in the female . J Med Genet . 1988;25:589-595.Crossref 60. Reik W. Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea . J Med Genet . 1988;25:805-808.Crossref 61. Davidson EA, Robertson EE. Alzheimer's disease in one monozygotic twin . J Neurol Neurosurg Psychiatry . 1955;35:707-722. 62. Jarvik LF, Ruth V, Matsuyama SS. Organic brain syndrome and aging: a six-year follow-up of surviving twins . Arch Gen Psychiatry . 1980;37:280-286.Crossref 63. Cook RH, Schneck SA, Clark DB. Twins with Alzheimer's disease . Arch Neurol . 1981;38:300-301.Crossref 64. Nee LE, Eldridge R, Sunderland T, et al. Dementia of the Alzheimer type: clinical and family study of 22 twin pairs . Neurology . 1987;37:359-363.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Association of Decreased Paternal Age and Late-Onset Alzheimer's Disease: An Example of Genetic Imprinting?

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References (73)

Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1991.00530180051017
Publisher site
See Article on Publisher Site

Abstract

Abstract • Several studies have identified advanced maternal age as a risk factor for Alzheimer's disease. This study evaluated maternal and paternal age at birth of 237 patients with Alzheimer's disease, each of whom was matched to five control subjects based on sex, year of birth, survival age, and location of residence. It was found that decreased paternal age substantially increased the susceptibility to the common form of Alzheimer's disease that occurs after the age of 67 years, whereas advanced maternal age had a negligible effect on risk of Alzheimer's disease. The higher incidence of late-onset Alzheimer's disease among persons born to younger fathers is consistent with a genetic imprinting mechanism involving DNA methylation. The proposed model postulates a role for environmental agents in the pathogenesis of Alzheimer's disease and accounts for families that show an aggregation of cases but no apparent pattern of inheritance. References 1. Evans DA, Funkenstein HH, Albert MS, et al. Prevalence of Alzheimer's disease in a community population of older persons . JAMA . 1989;262:2551-2556.Crossref 2. Goudsmit J, Morrow CH, Asher DM, et al. Evidence for and against transmissibility of Alzheimer's disease . Neurology . 1980;30:945-950.Crossref 3. Mortimer JA, French LR, Hutton JT, Schuman LM. Head injury as a risk factor for Alzheimer's disease . Neurology . 1985;35:264-267.Crossref 4. Crapper McLachlan DR. Aluminum and Alzheimer's disease . Neurobiol Aging . 1986;7:525-532.Crossref 5. Birchall JD, Chappall JS. Aluminum, chemical physiology, Alzheimer's disease . Lancet . 1988;2:1008-1010.Crossref 6. Manuelidis EE, de Figueredo JM, Kim JH, Fritch WW, Manuelidis L. Transmission studies from blood of Alzheimer disease patients and healthy relatives . Proc Natl Acad Sci U S A . 1988;85:4898-4901.Crossref 7. Martyn CN, Barker DJP, Osmond C, Harris EC, Edwardson JA, Jacey RF. Geographical relation between Alzheimer's disease and aluminum in the drinking water . Lancet . 1989;1:59-62. 8. Haberland G. Alzheimer's disease in Down's syndrome . Acta Neurol Belg . 1969;69:369-380. 9. Heston LL. Alzheimer's disease, trisomy 21, and myeloproliferative disorders: associations suggesting a genetic diathesis . Science . 1977;196:322-323.Crossref 10. Ellis WG, McCulloch JR, Corley CL. Presenile dementia in Down's syndrome: ultrastructural identity with Alzheimer's disease . Neurology . 1974;24:101-106.Crossref 11. Wisniewski K, Howe J, Williams DG, Wisniewski HM. Precocious aging and dementia in patients with Down's syndrome . Biol Psychiatry . 1978;13:619-627. 12. Mann DMA. The pathological association between Down syndrome and Alzheimer disease . Mech Ageing Dev . 1988;43:99-136.Crossref 13. Penrose LS. The relative effects of paternal and maternal age in mongolism . J Genet . 1933;27:219-224.Crossref 14. Cohen D, Eisdorfer C, Leverenz J. Alzheimer's disease and maternal age . J Am Geriatr Soc . 1982;30:656-659. 15. Whalley LJ, Carothers AD, Collyer S, De Mey R, Frackiewicz A. A study of familial factors in Alzheimer's disease . Br J Psychiatry . 1982;140:249-256.Crossref 16. Amaducci LA, Fratiglioni L, Rocca WA, et al. Risk factors for clinically diagnosed Alzheimer's disease: a case-control study of an Italian population . Neurology . 1986;36:922-931.Crossref 17. Urakami K, Adachi Y, Takahashi K. A community-based study of parental age at the birth of patients with dementia of the Alzheimer type . Arch Neurol . 1989;46:38-39.Crossref 18. Corkin S, Growdon JH, Rasmussen SL. Parental age as a risk factor in Alzheimer's disease . Ann Neurol . 1983;13:674-676.Crossref 19. Heyman A, Wilkinson WE, Hurwitz BJ, et al. Alzheimer's disease: genetic aspects and associated clinical disorders . Ann Neurol . 1983;14:507-515.Crossref 20. English D, Cohen D. A case-control study of maternal age in Alzheimer's disease . J Am Geriatr Soc . 1985;33:167-169. 21. White JA, McGue M, Heston LL. Fertility and parental age in Alzheimer's disease . J Gerontol . 1986;41:40-43.Crossref 22. Khachaturian ZS. Diagnosis of Alzheimer's disease . Arch Neurol . 1985;42:1097-1105.Crossref 23. McKhann G, Drachmann D, Folstein M, Katzman R, Price D, Stadlan D. 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;34:939-945.Crossref 24. Farrer LA, O'Sullivan DM, Cupples LA, Growdon JH, Myers RH. Assessment of genetic risk for Alzheimer's disease among first-degree relatives . Ann Neurol . 1989;25:485-493.Crossref 25. Dawber TR, Meadors GF, Moore FE. Epidemiological approaches to heart disease: the Framingham Study . Am J Public Health . 1951;41:279-286.Crossref 26. Schildkraut JM, Myers RH, Cupples LA, Kiely DJ, Kannel WB. Coronary risk associated with age and sex of parental heart disease in the Framingham study . Am J Cardiol . 1989;64:555-559.Crossref 27. Gail M, Williams R, Byar DP, Brown C. How many controls? J Chronic Dis . 1976;29:723-731.Crossref 28. Sokal RR, Rohlf RJ. Biometry . 2nd ed. New York, NY: WH Freeman & Co; 1981. 29. Chui HC, Teng EL, Henderson VW, Moy AC. Clinical subtypes of dementia of the Alzheimer type . Neurology . 1985;35:1544-1550.Crossref 30. Mayeux R, Stern Y, Spanton S. Heterogeneity in dementia of the Alzheimer type: evidence of subgroups . Neurology . 1985;35:453-461.Crossref 31. Farrer LA, Myers RH, Cupples LA, et al. Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity . Neurology . 1990;40:395-403.Crossref 32. St George-Hyslop PH, Myers RH, Haines JL, et al. Familial Alzheimer's disease: progress and problems . Neurobiol Aging . 1989;10:417-425.Crossref 33. Breslow NE, Day NE, Halvorsen KT, Prentice RL, Sabai C. Estimation of multiple relative risk functions in matched case-control studies . Am J Epidemiol . 1978;108:299-307. 34. SAS User's Guide: Statistics . Cary, NC: SAS Inc; 1986. 35. White L, Wolf PA, Farmer M, et al. Neuropsychologic test performance in later life: a cross-sectional study of the Framingham Heart Study cohort . Am J Epidemiol . 1983;118:444. Abstract. 36. Hassold TJ, Jacobs PA. Trisomy in man . Annu Rev Genet . 1984;18:69-67.Crossref 37. Buckton KE, Whalley LJ, Lee M, Christie JE. Chromosome changes in Alzheimer's presenile dementia . J Med Genet . 1983;20:46-51.Crossref 38. St George-Hyslop P, Tanzi RE, Polinsky RJ, et al. The genetic defect causing familial Alzheimer's disease maps on chromosome 21 . Science . 1987;235:885-890.Crossref 39. Goate AM, Haynes AR, Owen MJ, et al. Predisposing locus for Alzheimer's disease on chromosome 21 . Lancet . 1989;1:352-355.Crossref 40. Van Broeckhoven C, Van Hul W, Backhovens H, et al. The familial Alzheimer's disease gene is located close to the centromere on chromosome 21 . Am J Hum Genet . 1988;43( (suppl) ):A205. Abstract. 41. St George-Hyslop PH, Haines JL, Farrer LA, et al. Genetic linkage studies suggest that Alzheimer's disease is not a single homogeneous disorder . Nature . 1990;347:194-197.Crossref 42. Delabar JM, Goldgaber D, Lamour Y, et al. β Amyloid gene duplication in Alzheimer's disease and karyotypically normal Down syndrome . Science . 1987;235:1390-1392.Crossref 43. Schweber M, Tuson C, Shiloh R, Ben-Neriah Z. Triplication of chromosome 21 material in Alzheimer's disease . Neurology . 1987;37( (suppl 1) ):222. Abstract. 44. St George-Hyslop PH, Tanzi RE, Polinsky RJ, et al. Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease . Science . 1987;238:664-666.Crossref 45. Tanzi RE, Bird ED, Latt SA, Neve RL. The amyloid β protein gene is not duplicated in brains from patients with Alzheimer's disease . Science . 1987;238:666-669.Crossref 46. Berman M, Lee G, Selkoe DJ. Gene dosage of the amyloid β precursor protein in Alzheimer's disease . Science . 1987;238:669-671.Crossref 47. Hall JG. Genomic imprinting: review and relevance to human diseases . Am J Hum Genet . 1990;46:857-873. 48. Hadchouel M, Farza H, Simon D, Tiollias P, Poucel C. Maternal inhibition of hepatitis B surface antigen gene expression in transgenic mice correlates with de novo methylation . Nature . 1987;329:454-456.Crossref 49. Monk M, Boubelik M, Lehnert S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse development . Development . 1987;99:371-382. 50. Reik W, Collick A, Norris ML, Barton SC, Surani MAH. Genomic imprinting determines methylation of parental alleles in transgenic mice . Nature . 1987;328:248-251.Crossref 51. Sapienza C, Peterson AC, Rossant J, Balling R. Degree of methylation of transgenes is dependent on gamete of origin . Nature . 1987;328:251-254.Crossref 52. Swain JL, Stewart TA, Leder P. Parental legacy determines methylation and expression of an autosomal transgene: a molecular mechanism for parental imprinting . Cell . 1987;50:719-727.Crossref 53. Holliday R. A different kind of inheritance . Sci Am . (June) 1989:60-73. 54. Vogel F, Rathenberg R. Spontaneous mutation in man . Adv Hum Genet . 1975;5:223-318. 55. Berg L. Does Alzheimer's disease represent an exaggeration of normal aging? Arch Neurol . 1985;42:737-739.Crossref 56. Mann DMA, Yates PO, Marcyniuk B. Alzheimer's presenile dementia, senile dementia of the Alzheimer type and Down's syndrome in middle age form an age related continuum of pathological changes . Neuropathol Appl Neurobiol . 1985;10:185-207.Crossref 57. Brayne C, Calloway P. Normal ageing, impaired cognitive function, and senile dementia of the Alzheimer's type: a continuum? Lancet . 1988;1:1265-1267.Crossref 58. Farrer LA. Genetic neurodegenerative disease models for human aging . In: Rothstein M, ed. Review of Biological Research in Aging . New York, NY: Alan R Liss Inc; 1987;3:163-189. 59. Ridley RM, Frith CD, Crow TJ, Conneally PM. Anticipation in Huntington's disease is inherited through the male line but may originate in the female . J Med Genet . 1988;25:589-595.Crossref 60. Reik W. Genomic imprinting: a possible mechanism for the parental origin effect in Huntington's chorea . J Med Genet . 1988;25:805-808.Crossref 61. Davidson EA, Robertson EE. Alzheimer's disease in one monozygotic twin . J Neurol Neurosurg Psychiatry . 1955;35:707-722. 62. Jarvik LF, Ruth V, Matsuyama SS. Organic brain syndrome and aging: a six-year follow-up of surviving twins . Arch Gen Psychiatry . 1980;37:280-286.Crossref 63. Cook RH, Schneck SA, Clark DB. Twins with Alzheimer's disease . Arch Neurol . 1981;38:300-301.Crossref 64. Nee LE, Eldridge R, Sunderland T, et al. Dementia of the Alzheimer type: clinical and family study of 22 twin pairs . Neurology . 1987;37:359-363.Crossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Jun 1, 1991

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