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Evidence for Allelic Heterogeneity in Familial Early-Onset Alzheimer's Disease

Published online by Cambridge University Press:  03 January 2018

Cornelia M. Van Duijn ,
Christine Van Broeckhoven ,
John A. Hardy ,
Alison M. Goate ,
Martin N. Rossor ,
Anton Vandenberghe ,
J-J. Martin ,
Albert Hofman  and
Michael J. Mullan
Cornelia M. Van Duijn
Affiliation:
Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, the Netherlands
Christine Van Broeckhoven
Affiliation:
Department of Biochemistry, University of Antwerp, Belgium
John A. Hardy
Affiliation:
Department of Biochemistry, St Mary's Hospital Medical School, University of London
Alison M. Goate
Affiliation:
Department of Biochemistry, St Mary's Hospital Medical School
Martin N. Rossor
Affiliation:
Department of Neurology, St Mary's Hospital Medical School
Anton Vandenberghe
Affiliation:
Department of Biochemistry, University of Antwerp
J-J. Martin
Affiliation:
Department of Neurology and Neuropathology, Born-Bunge Foundation, University of Antwerp
Albert Hofman
Affiliation:
Department of Epidemiology and Biostatistics, Erasmus University Medical School, The Netherlands
Michael J. Mullan*
Affiliation:
Department of Biochemistry, University of Antwerp, Department of Neurology, St Mary's Hospital Medical School
*
∗Department of Biochemistry, St Mary's Hospital Medical School, University of London, Norfolk Place, London W2 1PG
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Abstract

Age of onset was examined for 139 members of 30 families affected by early-onset AD. Most (77%) of the variance of age of onset derived from differences between rather than within families. The constancy of age of onset within families was also observed in an analysis restricted to families derived from a population-based epidemiological study with complete ascertainment of early-onset AD. Furthermore, we observed clustering of age of onset within those families that support linkage to the predisposing locus on chromosome 21. Our data are compatible with the view that allelic heterogeneity at the AD locus may account for the similarity in age of onset within families. This finding may be of value for scientific studies of AD as well as for genetic counselling.

Type
Review Article
Information
The British Journal of Psychiatry , Volume 158 , Issue 4 , April 1991 , pp. 471 - 474
Copyright
Copyright © Royal College of Psychiatrists, 1991 

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References

Cook, R. H., Ward, B. E. & Austin, J. H. (1979) Studies in aging of the brain: IV. Familial Alzheimer disease: relation to transmissible dementia, aneuploidy and microtubular defects. Neurology, 29, 1402–1412.CrossRefGoogle ScholarPubMed
Farrer, L. A., Myers, R. H., Crupples, L. A., et al (1990) Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity. Neurology, 40, 395–403.CrossRefGoogle ScholarPubMed
Folstein, M. F., Warren, A. & McHugh, P. R. (1988) Heterogeneity in Alzheimer's disease: an exercise in the resolution of a phenotype. In Genetics and Alzheimer's Disease (eds P. M. Sinet, Y. Lamour & Y. Christen), pp. 5–12. London: Springer-Verlag.Google Scholar
Foncin, J-F., Salmon, D. & Bruni, A. C. (1986) Genetics of Alzheimer's disease: a large kindred with apparent Mendelian transmission; possible implications for a linkage study. In New Concepts in Alzheimer's Disease (eds M. Briley, A. Kato & M. Weber), pp. 242–256. London: Macmillan.Google Scholar
Goate, A. M., Haynes, A. R., Owens, M. J., et al (1989) Predisposing locus for Alzheimer's disease on chromosome 21. Lancet, i, 352–355.Google 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 the Neurological Sciences, 49, 79–89.CrossRefGoogle ScholarPubMed
Hofman, A., Schulte, W., Tanja, T. A., et al (1989) History of dementia and Parkinson's disease in 1st-degree relatives of patients with Alzheimer's disease. Neurology, 39, 1589–1592.Google Scholar
Huff, F. J., Auerbach, J., Chakravarti, A., et al (1988) Risk of dementia in relatives of patients with Alzheimer's disease. Neurology, 38, 786–790.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 the Department of Health and Human Services Task Force on Alzheimer's disease. Neurology, 34, 939–944.Google Scholar
Nee, L. E., Polinsky, R. J., Eldridoe, R., et al (1983) A family with histologically confirmed Alzheimer's disease. Archives of Neurology, 40, 203–208.CrossRefGoogle ScholarPubMed
Smith, C. (1975) Quantitative inheritance. In Textbook of Human Genetics (eds G. Fraser & O. Mayo), pp. 382–391. Oxford: Blackwell Scientific.Google Scholar
StGeoroe-Hyslop, P. H., Tanzi, R. E., Polinsky, R. J., et al (1987) The genetic defect causing familial Alzheimer's disease maps on chromosome 21. Science, 235, 885–890.Google Scholar
Van Broeckhoven, C., Backhovens, H., Van Hul, W., et al (1991) Genetic linkage analysis in early onset familial Alzheimer's dementia. In Neuropsychopharmacology Proceedings of the XVIth CINP Congress (eds W. E. Bunney Jr, J. Hippius, G. Laakmann, et al), pp. 86–91. Berlin: Springer-Verlag.Google Scholar
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