Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.

摘要: A genetic component in the etiology of Alzheimer disease (AD) has been supported by indirect evidence for several years, with autosomal dominant inheritance age-dependent penetrance being suggested to explain familial aggregation affecteds. St. George Hyslop et al. reported linkage AD (FAD) four early-onset families (mean age at onset [M] less than 50 years). Subsequent studies have inconsistent their results; Goate also positive lod scores. However, both Pericak-Vance al.'s study a series mainly late-onset FAD (M greater 60 years) and Schellenberg failed confirm chromosome 21 (CH21). These various suggest possibility heterogeneity, some linked CH21 others unlocalized. Recently, extended analysis include additional families. The analyses earlier finding CH21, while showing strong heterogeneity between 65 Because our did not show we undertook genomic search an locus FAD. confounding factor late lack clear Mendelian transmission families, employed affected-pedigree-member (APM) method as initial screen possible linkage. Using this method, identified two regions suggesting linkage: proximal long arm 19 (CH19) region Application standard likelihood (LOD score) these data support gene locate on CH19, particularly further delineate CH19 area needing investigation