Alzheimer Disease 10


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


In an extended multiplex family, ascertained in a population-based study of early-onset AD in the northern Netherlands, Rademakers et al. (2005) obtained conclusive evidence of linkage of AD with a candidate region of 19.7 cM at 7q36. They identified a shared haplotype at 7q36 between the index family and 3 of 6 multiplex AD-affected families from the same geographic region, which was indicative of a founder effect and defined a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified only an exonic silent mutation in the PAXIP1 gene (608254), 38030G-C in the exon 10 genomic sequence, which affected codon 626. It remained to be determined whether PAXIP1 has a functional role in the expression of AD in the index family or whether another mutation at this locus explained the observed linkage and sharing. Association data in a population-based early-onset AD patient-control sample strongly supported the linkage data from the informative index family indicating a novel AD locus at 7q36. The genetic heterogeneity of AD was emphasized. It is noteworthy that another gene in the 7q36 region, NOS3 (163729), has also been associated with Alzheimer disease.