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Genetics, Alzheimer's Disease and Senile Dementia

Published online by Cambridge University Press:  02 January 2018

D. W. K. Kay
D. W. K. Kay*
Affiliation:
Medical Research Council Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
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Abstract

Genetic factors in the aetiology of Alzheimer's disease (AD), are now being intensively investigated. The homogeneity of AD is under investigation. There are a few large kindreds with early onset of AD in whom transmission appears to be typically autosomal dominant, and 65% or more of the remaining cases at any age may have genetic aetiology. Both multifactorial and autosomal dominant inheritance with age-dependent expression have been proposed, but the late onset and death of unaffected relatives from competing causes make it difficult to choose between them. Lifetime risk gives the best estimate of incidence in family studies, but clinical and pathological criteria are not clear enough for confident diagnosis of AD in late old age. A role for external factors is indicated by twin studies, and the role of aluminium is currently under investigation. Molecular genetics promises to resolve many questions. The clinicians' role will be to provide well documented families for interdisciplinary research and to help in clarifying diagnosis in late old age.

Type
Review Articles
Information
The British Journal of Psychiatry , Volume 154 , Issue 3 , March 1989 , pp. 311 - 320
Copyright
Copyright © Royal College of Psychiatrists, 1989 

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References

Bahmanyar, S., Higgins, G. A., Goldgaber, D., et al (1987) Localization of amyloid β protein messenger RNA in brains from patients with Alzheimer's disease. Science, 237, 77–80.Google Scholar
Baker, H. F., Ridley, R. M. & Crow, T. J. (1985) Experimental transmission of an autosomal dominant spongiform encephalopathy: does the infectious agent originate in the human genome? British Medical Journal, 291, 299–302.CrossRefGoogle ScholarPubMed
Baron, M. & Rainer, J. D. (1988) Molecular genetics and human disease: implications for modern psychiatric research and practice. British Journal of Psychiatry, 152, 741–753.Google Scholar
Blessed, G. (1984) Clinical features and neuropathological correlations of Alzheimer-type disease. In Handbook of Studies on Psychiatry and Old Age (eds Kay, D. W. K. & Burrows, G. D.), pp. 133–143. Amsterdam: Elsevier.Google Scholar
Brayne, C. & Calloway, P. (1988) Normal ageing, impaired cognitive function, and senile dementia of the Alzheimer's type: a continuum? Lancet, i, 1265–1267.CrossRefGoogle Scholar
Breitner, J. C. S. (1987) Genetic factors in the etiology of Alzheimer's disease. In Psychopharmacology: the Third Generation of Progress (ed. Meltzer, H. Y.), pp. 929–939. New York: Raven Press.Google Scholar
Breitner, J. C. S. & Folstein, M. F. (1984) Familial Alzheimer dementia: a prevalent disorder with specific clinical features. Psychological Medicine, 14, 63–80.Google Scholar
Breitner, J. C. S., Folstein, M. F. & Murphy, E. A. (1986a) Familial aggregation in Alzheimer dementia I. A model for the age-dependant expression of an autosomal dominant gene. Journal of Psychiatric Research, 20, 31–43.CrossRefGoogle Scholar
Breitner, J. C. S., Murphy, E. A. & Folstein, H. F. (1986b) Familial aggregation of Alzheimer disease II. Clinical genetic implications of age-dependent onset. Journal of Psychiatric Research, 20, 45–55.CrossRefGoogle ScholarPubMed
Breitner, J. C. S., Murphy, E. A., Silverman, J. M., et al (1988a) The age-dependent expression of familial risk in Alzheimer's disease. American Journal of Epidemiology, 128, 536–548.Google Scholar
Breitner, J. C. S., Silverman, J. M., Mohs, R. C., et al (1988b) Familial aggregation in Alzheimer's disease: comparison of risk among relatives of early and late-onset cases, and among male and female relatives in successive generations. Neurology, 38, 207–212.Google Scholar
Candy, J., Oakley, A., Klinowski, J., et al (1986a) Aluminosilicates and senile plaque formation in Alzheimer's disease. Lancet, i, 354–357.CrossRefGoogle Scholar
Candy, J., Oakley, A., Gauvreau, D., et al (1988) Association of aluminium and silicon with neuropathological changes in the ageing brain. Interdisciplinary Topics in Gerontology, 25, 1–16.Google Scholar
Chandra, V., Philipose, V., Bell, P. A., et al (1987) Case-control study of late onset “probable Alzheimer's disease”. Neurology, 37, 1295–1300.Google Scholar
Chase, G. A., Folstein, M. F., Breitner, J. C. S., et al (1983) The use of life tables and survival analysis in testing genetic hypotheses, with an application to Alzheimer's disease. American Journal of Epidemiology, 117, 590–597.Google Scholar
Chase, G. A. & Kramer, M. (1986) The abridged census method as an estimator of lifetime risk. Psychological Medicine, 16, 865–871.Google Scholar
Chui, H. C., Teng, E. L., Henderson, V. W., et al (1985) Clinical subtypes of dementias of the Alzheimer type. Neurology, 35, 1544–1550.Google Scholar
Cook, R. H., Ward, B. E. & Austin, J. H. (1979) IV. Familial Alzheimer disease: relation to transmissible dementia, aneuploidy, and microtubular defects. Neurology, 29, 1402–1412.Google Scholar
Cook, R. H., Schneck, S. A. & Clark, D. B. (1981) Twins with Alzheimer's disease. Archives of Neurology, 38, 300–301.Google Scholar
Corsellis, J. N. A. (1986) The transmissibility of dementia. British Medical Bulletin, 42, 111–114.Google Scholar
Crapper McLachlan, D. R. (1986) Aluminium and Alzheimer's disease. Neurobiology of Aging, 7, 525–532.Google Scholar
Davies, P. (1986) The genetics of Alzheimer's disease: a review and a discussion of the implications. Neurobiology of Aging, 7, 459–466.Google Scholar
Delabar, J-M., Goldgaber, D., Lamour, Y., et al (1987) β Amyloid gene duplication in Alzheimer's disease and karyotypically normal Down syndrome. Science, 235, 1390–1392.Google Scholar
Embry, C. & Lippmann, S. (1985) Presumed Alzheimer's disease beginning at different ages in two twins. Journal of the American Geriatrics Society, 33, 61–62.Google Scholar
Erlich, S. S. & Davis, R. L. (1980) Alzheimer's disease in the very aged. Journal of Neuropathology and Experimental Neurology, 39, 352.Google Scholar
Feldman, R. G., Chandler, K. A., Levy, L. L., et al (1963) Familial Alzheimer's disease. Neurology, 13, 811–824.CrossRefGoogle ScholarPubMed
Flaten, T. P. (1989) Geographical association between aluminium in drinking water and death rates with dementia (including Alzheimer's disease), Parkinson's disease and amyotrophic lateral sclerosis in Norway. Journal of Environmental Geochemistry & Health (suppl.) (in press).Google Scholar
Foncin, J. F., Salmon, D., Supino-Viterbo, V., et al (1985) Démence présénile d'Alzheimer transmise dans une famille étendue. Revue Neurologie (Paris), 141, 194–202.Google Scholar
Garruto, R., Swyt, C., Yanagihara, R., et al (1986) Intraneuronal co-localisation of silicon with calcium and aluminium in amyotrophic lateral sclerosis and parkinsonism with dementia of Guam. New England Medical Journal, 315, 711–712.Google Scholar
Goldgaber, D., Lerman, M. I., McBride, O. W., et al (1987) Characterisation and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science, 235, 877–880.Google Scholar
Goudsmit, J. (1982) Transmissibility of Alzheimer's disease. American Journal of Psychiatry, 39, 1380–1381.CrossRefGoogle Scholar
Goudsmit, J., White, B. J., Weitkamp, L. R., et al (1981) Familial Alzheimer's disease in two kindreds of the same geographic and ethnic origin. Journal of Neurological Sciences, 48, 79–89.Google Scholar
Guiroy, D. C., Miyazaki, M., Multhaup, G., et al (1987) Amyloid of neurofibrillary tangles of Guamanian parkinsonism –dementia and Alzheimer disease share identical amino acid sequence. Proceedings of the National Academy of Sciences, USA, 84, 2073–2077.Google Scholar
Gusella, J. F. (1986) The molecular genetic approach to familial Alzheimer's disease. Neurobiology of Aging, 7, 471–473.Google Scholar
Hagnell, O., Lanke, J., Rorsman, B., et al (1983) Current trends in the incidence of senile and multi-infarct dementia. Archives of Psychiatry and Neurological Sciences, 233, 423–438.Google Scholar
Hardy, J. A., Mann, D. M., Wester, P., et al (1986) An integrative hypothesis concerning the pathogenesis and progression of Alzheimer's disease. Neurobiology of Aging, 7, 489–502.Google Scholar
Henderson, A. S. (1988) The risk factors for Alzheimer's disease: a review and a hypothesis. Acta Psychiatrica Scandinavica, 78, 257–275.CrossRefGoogle ScholarPubMed
Heston, L. L. (1985) Alzheimer's disease and Down's syndrome: new insights. NIH conference. Annals of Internal Medicine, 103, 566–570.Google Scholar
Heston, L. L. (1988) Morbid risk in first-degree relatives of persons with Alzheimer's disease. Archives of General Psychiatry, 45, 97–98.Google Scholar
Heston, L. L. & White, J. (1978) Pedigrees of 30 families with Alzheimer's disease: associations with defective organization of microfilaments and microtubules. Behavior Genetics, 8, 315–331.Google Scholar
Heston, L. L., Mastri, A. R., Anderson, V. E., et al (1961) Dementia of the Alzheimer type. Archives of General Psychiatry, 38, 1085–1090.Google Scholar
Heyman, A., Wilkinson, W. E., Hurwitz, B. J., et al (1983) Alzheimer's disease: genetic aspects and associated clinical disorders. Annals of Neurology, 14, 507–515.Google Scholar
Jarvik, L. F., Ruth, V., & Matsuyama, S. S. (1980) Organic brain syndrome and aging: a six-year follow-up of surviving twins. Archives of General Psychiatry, 37, 280–286.Google Scholar
Kang, J., Lemaire, H-G., Unterbeck, A., et al (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325, 733–736.Google Scholar
Kay, D. W. K. (1986) The genetics of Alzheimer's disease. British Medical Bulletin, 42, 19–23.Google Scholar
Kitaguchi, N., Takahashi, Y., Tokushima, Y., et al (1988) Novel precursor of Alzheimer's disease amyloid protein shows protease inhibitory activity. Nature, 331, 530–532.Google Scholar
Larsson, T., Sjögren, T. & Jacobson, G. (1963) Senile dementia. Acta Psychiatrica Scandinavica (suppl. 167).Google Scholar
Martyn, C. N. (1988) Aluminium and Alzheimer's disease: an epidemiological approach. Journal of Environmental Geochemistry and Health, suppl. (in press)Google Scholar
Masters, C. L., Gajdusek, C. & Gibbs, C. J. (1981a) The familial occurrence of Creutzfeldt-Jacob disease and Alzheimer's disease. Brain, 104, 535–558.Google Scholar
Masters, C. L., Gajdusek, C., Gibbs, C. J., (1981b) Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Sträussler syndrome. Brain, 104, 535–558.Google Scholar
Masters, C. L., Multhaup, G., Simms, G., et al (1985a) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. Embo Journal, 4, 2757–2763.CrossRefGoogle ScholarPubMed
Masters, C. L., Simms, G., Weinman, N. A., et al (1985b) Amyloid plaque core protein in Alzheimer's disease and Down syndrome. Proceedings of the National Academy of Sciences, USA, 82, 4245–4249.CrossRefGoogle ScholarPubMed
Matsuyama, S. S., Jarvik, L. F. & Kumar, V. (1985) In Recent Advances in Psychogeriatrics (ed. Arie, T.), pp. 45–69. London: Churchill Livingstone.Google Scholar
McKhann, G., Drachman, D., Folstein, M., et al (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health & Human Services task force on Alzheimer's disease. Neurology, 34, 939–944.CrossRefGoogle ScholarPubMed
Mohs, R. C., Breitner, J. C. S., Silverman, J. M., et al (1987) Alzheimer's disease: morbid risk among first degree relatives approximates 50% by 90 years of age. Archives of General Psychiatry, 44, 405–408.CrossRefGoogle ScholarPubMed
Morris, J. C., Cole, M., Banker, B. Q., et al (1984) Hereditary dysphasic dementia and the Pick-Alzheimer spectrum. Annals of Neurology, 16, 455–466.Google Scholar
Nee, L. E., Polinsky, R. J., Eldridge, R., et al (1983) A family with histologically confirmed Alzheimer's disease. Archives of General Psychiatry, 40, 203–208.Google Scholar
Nee, L. E., Eldridge, R., Sunderland, T., et al (1987) Dementia of the Alzheimer type: clinical and family study of 22 twin pairs. Neurology, 37, 359–363.Google Scholar
Nerl, C. N., Mayeux, R. & O'Neill, G. J. (1984) HLA-linked complement markers in Alzheimer's and Parkinson's disease: C4 variant (C4B2) a possible marker for senile dementia of the Alzheimer type. Neurology, 34, 310–314.Google Scholar
Peress, N. S., Kane, W. C. & Aronsson, S. M. (1973) Central nervous system findings in a tenth decade autopsy population. Progress in Brain Research, 40, 480–483.Google Scholar
Podlisny, M. B., Lee, G. & Selkoe, D. J. (1988) Gene dosage of the β-amyloid precursor protein in Alzheimer's disease. Science, 238, 669–671.Google Scholar
Ponte, P., Gonzalez-de-Whitt, P., Schilling, J., et al (1988) A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature, 331, 525–527.Google Scholar
Powell, D. & Folstein, M. F. (1984) Pedigree study of familial Alzheimer disease. Journal of Neurogenetics, 1, 189–197.Google Scholar
Quinn, N. P., Rossor, M. N. & Marsden, C. D. (1986) Dementia and Parkinson's disease – pathological and neurological considerations. British Medical Bulletin, 42, 86–90.Google Scholar
Renvoize, E. B. (1984) An HLA and family study of Alzheimer's disease. Psychological Medicine, 14, 515–520.Google Scholar
Robbins, J. H., Otsuka, F., Tarone, R. E., et al (1984) Parkinson's disease and Alzheimer's disease: hypersensitivity to X rays in cultured cell lines. Journal of Neurology, Neurosurgery and Psychiatry, 48, 916–923.Google Scholar
Roberts, E. (1986) Alzheimer's disease may begin in the nose and may be caused by aluminosilicates. Neurobiology of Aging, 7, 561–567.Google Scholar
Rocca, W. A., Amaducci, L. A. & Schoenberg, B. S. (1986) Epidemiology of clinically diagnosed Alzheimer's disease. Annals of Neurology, 19, 415–424.Google Scholar
Roses, A. D. (1986) Alzheimer's disease: new genetic research strategies. Neurobiology of Aging, 7, 466–468.Google Scholar
Roses, A. D., Pericap-Vance, M. M., Haynes, C. S. et al (1988) Genetic linkage studies in Alzheimer's disease (AD). Neurology (supp. 1), 38, 173.Google Scholar
Roth, M. & Wischik, C. (1985) The heterogeneity of Alzheimer's disease and its implications for scientific investigations of the disorder. In Recent Advances in Psychogeriatrics (ed. Arie, T.), pp. 71–92. London: Churchill Livingstone.Google Scholar
St George-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., et al (1987a) The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science, 235, 885–890.Google Scholar
St George-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., et al (1987b) Absence of duplication of chromosome 21 genes in familial and sporadic Alzheimer's disease. Science, 238, 664–666.Google Scholar
St George-Hyslop, P. H., Tanzi, R. E., Hobbs, W., et al (1987c) DNA markers in familial Alzheimer's disease. In Proceedings International Symposium on New Concepts in Alzheimer's disease, pp. 257–264. Pierre Fabre Monograph Series. London: MacMillan.Google Scholar
Schellenberg, G. D., Bird, T. D. & Wijsman, E. M. (1988) Absence of linkage of chromosome 21q21 markers to familial Alzheimer's disease. Science, 241, 1507–1510.Google Scholar
Schweber, M. A. (1985) A possible unitary genetic hypothesis for Alzheimer's disease and Down's syndrome. Annals of the New York Academy of Science, 450, 223–238.Google Scholar
Scudiero, D. A., Polinsky, R. J., Brumback, R. A., et al (1986) Alzheimer disease fibroblasts are hypersensitive to the lethal effects of a DNA-damaging chemical. Mutation Research, 159, 125–131.Google Scholar
Selkoe, D. J., Bell, D. S., Podlisny, M. B., et al (1987) Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease. Science, 235, 873–877.Google Scholar
Sharman, M. G., Watt, D. C., Janota, I., et al (1979) Alzheimer's disease in a mother and identical twin sons. Psychological Medicine, 9, 771–774.Google Scholar
Silverman, J. M., Breitner, J. C. S., Mohs, R. C., et al (1986) The reliability of the family history method in Alzheimer's disease and related dementias. American Journal of Psychiatry, 143, 1279–1282.Google Scholar
Sjögren, T., Sjögren, H. & Lindgren, B. G. H. (1952) Morbus Alzheimer and morbus Pick. Acta Psychiatrica Scandinavica Supplementum 82, 1–152.Google Scholar
Slater, E. & Cowie, V. (1971) Appendix D. In The Genetics of Mental Disorders. London: Oxford University Press.Google Scholar
Sluss, T. K., Gruenberg, E. M. & Kramer, M. (1981) The use of longitudinal studies in the investigation of risk factors for senile dementia–Alzheimer type. In The Epidemiology of Dementia (eds Mortimer, J. A. & Schuman, L. M.), pp. 132–154. New York: Oxford University Press.Google Scholar
Sturt, E. (1986) Application of survival analysis to the inception of dementia. Psychological Medicine, 16, 583–593.Google Scholar
Tanzi, R. E., Gusella, J. F., Watkins, P. C., et al (1987a) Amyloid β protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science, 235, 880–884.Google Scholar
Tanzi, R. E., St George-Hyslop, P. H., Haines, J. L., et al (1987b) The genetic defect in familial Alzheimer's disease is not tightly linked to the amyloid β-protein gene. Nature, 329, 156–157.Google Scholar
Tanzi, R. E., Bird, E. D., Latt, S. S., et al (1987c) The amyloid β protein gene is not duplicated in brain from patients with Alzheimer's disease. Science, 238, 666–668.CrossRefGoogle Scholar
Tanzi, R. E., McClatchey, A. I., Lamperti, E. D., et al (1988) Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer's disease. Nature, 331, 528–530.Google Scholar
Thompson, W. D. & Weissman, M. M. (1981) Quantifying lifetime risk of psychiatric disorder. Journal of Psychiatric Research, 16, 113–126.Google Scholar
Tomlinson, B. E. (1984) The pathology of Alzheimer's disease and senile dementia of the Alzheimer type. In Handbook of Studies on Psychiatry and Old Age (eds Kay, D. W. K. & Burrows, G. D.), pp. 89–117. Amsterdam: Elsevier.Google Scholar
Treves, T., Korczyn, A. D., Zilber, N., et al (1986) Presenile dementia in Israel. Archives of Neurology, 43, 26–29.Google Scholar
Van Broeckhoven, C., Genthe, A. M., van den Berghe, A., et al (1987) Failure of familial Alzheimer's disease to segregate with the A4-amyloid gene in several European families. Nature, 329, 153–155.Google Scholar
Wong, C. W., Quaranta, V. & Glenner, G. G. (1985) Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proceedings of the National Academy of Sciences, USA, 82, 8729–8732.Google Scholar
Wright, A. F. & Whalley, L. J. (1984) Genetics, ageing and dementia. British Journal of Psychiatry, 145, 20–38.Google Scholar
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