title: Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease.
abstract: Genetic studies have demonstrated very high heritability for Alzheimer's disease (AD) risk in humans; however, these genetic contributions have proven extremely challenging to map in large studies of AD patients. Processing of the amyloid precursor protein (APP) to produce amyloid-beta (Abeta) peptide is increasingly believed to be of central importance in AD pathogenesis. Intriguingly, mice from the C57BL/6J and DBA2/J inbred strains carrying the R1.40 APP transgene produce identical levels of unprocessed APP, but demonstrate significant, heritable differences in Abeta levels. To identify specific loci responsible for the observed genetic control of Abeta metabolism in this model system, we have performed a whole-genome quantitative trait locus (QTL) mapping experiment on a total of 516 animals from a C57BL/6JxDBA/2J intercross using a dense set of SNP genetic markers. Our studies have identified three loci on mouse chromosomes 1, 2, and 7 showing significant or suggestive associations with brain Abeta levels, several of which contain regions syntenic to previous reports of linkage in human AD.
authors.affiliation: Lerner Research Institute, Cleveland Clinic Foundation, Department of Neurosciences, NC3-164, 9500 Euclid Avenue, Cleveland, OH 44195 USA.
authors.forename: Davis
authors.initials: D
authors.lastname: Ryman
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Lamb
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable
chemical_list: D016229:Amyloid beta-Peptides