Alzheimer Disease 12


For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300.


Giedraitis et al. (2006) conducted a genome scan with 369 microsatellite markers in 12 extended families collected in Sweden. Age at disease onset ranged from 53 to 78 years, but in 10 of the families there was at least 1 member with age at onset of less than 65 years. Mutations in known early-onset Alzheimer disease susceptibility genes were excluded. All persons were genotyped for APOE (107741), but no clear linkage with the E4 allele was observed. Although no common disease locus could be found in all families, in 2 families an extended haplotype was identified on chromosome 8q shared by all affected members. In one of the families, nonparametric multimarker logarithm of the odds (lod) score of 4.2 (p = 0.004) was obtained. All 6 affected members of this family shared a haplotype of 10 markers spanning about 40 cM. The marker with the highest score was D8S1119. In another family, 3 affected members shared a haplotype in the same region. Giedraitis et al. (2006) proposed the existence of a dominantly acting Alzheimer disease susceptibility locus on chromosome 8p12-q22.