A POPULATION-BASED STUDY OF FAMILIAL ALZHEIMER-DISEASE - LINKAGE TO CHROMOSOME-14, CHROMOSOME-19, AND CHROMOSOME-21

Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19 , and 21 was studied in 10 families in which the disease was apparentl y inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD, Altho ugh 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 t o as ''LOAD''). Among the six families with early-onset AD (referred t o as ''EOAD,'' i.e., mean age of onset of AD of relatives was at or be fore age 65 years), conclusive linkage to 14q24.3 was found in one fam ily with a very early onset (around 47 years), while linkage to the sa me region was excluded in two other families. For the LOAD families, p redominantly negative lod scores were obtained, and the overall lod sc ore excluded linkage to chromosome 14. The results with markers on chr omosome 19 and chromosome 21 were not conclusive for EOAD and LOAD. Th e findings of our study confirm genetic heterogeneity within familial EOAD.