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

Davis Ryman, Yuan Gao, Bruce Lamb

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 (Aβ) 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 Aβ levels. To identify specific loci responsible for the observed genetic control of Aβ 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 × 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 Aβ levels, several of which contain regions syntenic to previous reports of linkage in human AD.

Original languageEnglish (US)
Pages (from-to)1190-1198
Number of pages9
JournalNeurobiology of Aging
Volume29
Issue number8
DOIs
StatePublished - Aug 2008
Externally publishedYes

Fingerprint

Genetic Loci
Amyloid
Amyloid beta-Protein Precursor
Alzheimer Disease
Chromosomes, Human, Pair 7
Chromosomes, Human, Pair 2
Chromosomes, Human, Pair 1
Quantitative Trait Loci
Amyloid beta-Peptides
Transgenes
Inbred C57BL Mouse
Genetic Markers
Single Nucleotide Polymorphism
Genome
Brain

Keywords

  • Abeta
  • Alzheimer
  • APP
  • Beta-amyloid
  • Genetics
  • Intercross
  • Mouse
  • QTL

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)

Cite this

Genetic loci modulating amyloid-beta levels in a mouse model of Alzheimer's disease. / Ryman, Davis; Gao, Yuan; Lamb, Bruce.

In: Neurobiology of Aging, Vol. 29, No. 8, 08.2008, p. 1190-1198.

Research output: Contribution to journalArticle

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