Alzheimer Disease 15


For a general phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease, see 104300.


Liu et al. (2007) conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that was conducted in an isolated population from the southwestern area of the Netherlands. Genealogic information resulted in an extremely large and complex pedigree of 4,645 members. The pedigree was split into 35 subpedigrees to reduce the computational burden of linkage analysis. They found significant evidence of linkage of AD to 3q22-q24 (AD15), in a region of 18 cM from D3S3514 to D3S3626 that reached a maximum hlod of 4.44 at marker D3S1579. Overall, multipoint analysis revealed 4 significant and 1 suggestive linkage peak. Liu et al. (2007) next tested for association between cognitive function and 4,173 single-nucleotide polymorphisms (SNPs) in the linked regions in an independent sample consisting of 197 individuals from the GRIP region. With use of cognitive function as an endophenotype of AD, the study indicated that potential disease-causing genes at 3q23 were the NMNAT3 (608702) and CLSTN2 genes.