van Duijn C M, Hendriks L, Farrer L A, Backhovens H, Cruts M, Wehnert A, Hofman A, Van Broeckhoven C
Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam.
Am J Hum Genet. 1994 Oct;55(4):714-27.
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.
在10个家庭中研究了阿尔茨海默病（AD）与14号、19号和21号染色体上DNA标记的连锁关系，这些家庭中该疾病显然以常染色体显性性状遗传。这些家庭来自荷兰一项基于人群的早发性AD流行病学研究。尽管所有先证者的AD发病年龄在65岁及以前，但在4个家庭中（称为“晚发性AD”，即LOAD）发病的平均年龄在65岁以后。在6个早发性AD家庭中（称为“早发性AD”，即EOAD，即亲属AD发病的平均年龄在65岁及以前），在1个发病非常早（约47岁）的家庭中发现与14q24.3有确凿的连锁关系，而在另外2个家庭中排除了与同一区域的连锁关系。对于LOAD家庭，主要获得了负的对数似然比分数，并且总体对数似然比分数排除了与14号染色体的连锁关系。关于19号染色体和21号染色体上标记的结果对于EOAD和LOAD尚无定论。我们的研究结果证实了家族性早发性AD中的遗传异质性。
