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Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was at or before age 65 years, the mean age at onset was after age 65 years in four families (referred to as "LOAD"). Among the six families with early-onset AD (referred to as "EOAD," i.e., mean age of onset of AD of relatives was at or before age 65 years), conclusive linkage to 14q24.3 was found in one family with a very early onset (around 47 years), while linkage to the same region was excluded in two other families. For the LOAD families, predominantly negative lod scores were obtained, and the overall lod score excluded linkage to chromosome 14. The results with markers on chromosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. The findings of our study confirm genetic heterogeneity within familial EOAD.

Type

Journal article

Journal

Am J Hum Genet

Publication Date

10/1994

Volume

55

Pages

714 - 727

Keywords

Aged, Aged, 80 and over, Alzheimer Disease, Chromosome Mapping, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 21, DNA Probes, Female, Genetic Linkage, Genetic Markers, Humans, Male, Middle Aged, Pedigree, Polymorphism, Restriction Fragment Length, Restriction Mapping