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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
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

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
Copyright
Copyright © Royal College of Psychiatrists, 1991 

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