Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:29

Article

Ryman, Davis^1,2  Gao, Yuan²  Lamb, Bruce T.^1,2,3 

[1] Cleveland Clin Fdn, Lerner Res Inst, Dept Neurosci, Cleveland, OH 44195 USA

[2] Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA

关键词: APP;    beta-amyloid;    Abeta;    Alzheimer;    genetics;    QTL;    mouse;    intercross;   

DOI  :  10.1016/j.neurobiolaging.2007.02.017

来源: Elsevier

【 摘 要 】

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 (A beta) 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 A beta levels. To identify specific loci responsible for the observed genetic control of A beta 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/6J x DBA/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 A beta levels, several of which contain regions syntenic to previous reports of linkage in human AD. (c) 2007 Elsevier Inc. All rights reserved.

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