Evidence for allelic heterogeneity in familial early-onset Alzheimer's disease.
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.
van Duijn
C M
CM
Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, The Netherlands.
van Broeckhoven
C
C
Hardy
J A
JA
Goate
A M
AM
Rossor
M N
MN
Vandenberghe
A
A
Martin
J J
JJ
Hofman
A
A
Mullan
M J
MJ
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002891:Chromosomes, Human, Pair 21; D005799:Genes, Dominant / Q000235:genetics*; D006580:Genetic Carrier Screening; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D012307:Risk Factors
D005819:Genetic Markers