Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome

Nicole Schupf, Annie Lee, Naeun Park, Lam Ha Dang, Deborah Pang, Alexander Yale, David Kyung Taek Oh, Sharon J. Krinsky-McHale, Edmund C. Jenkins, José A. Luchsinger, Warren B. Zigman, Wayne Silverman, Benjamin Tycko, Sergey Kisselev, Lorraine Clark, Joseph H. Lee

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1).

Original languageEnglish (US)
Pages (from-to)2907.e1-2907.e10
JournalNeurobiology of aging
Volume36
Issue number10
DOIs
StatePublished - Oct 1 2015

Keywords

  • Biomarkers
  • Down syndrome
  • Genetics
  • β Amyloid peptides

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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