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

Neurobiol Aging. 2015 Oct;36(10):2907.e1-10. doi: 10.1016/j.neurobiolaging.2015.06.020. Epub 2015 Jun 19.

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).

Keywords: Biomarkers; Down syndrome; Genetics; β Amyloid peptides.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Alzheimer Disease / genetics*
  • Amyloid beta-Peptides / blood*
  • Apolipoproteins E / genetics
  • Calcium Channels / genetics
  • DNA / genetics*
  • Down Syndrome / blood*
  • Down Syndrome / genetics*
  • Female
  • Genetic Association Studies*
  • Genotyping Techniques
  • Humans
  • Linear Models
  • Male
  • Membrane Glycoproteins / genetics
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis / methods
  • Peptide Fragments / blood
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface / genetics
  • Risk
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1

Substances

  • Amyloid beta-Peptides
  • Apolipoproteins E
  • CALHM1 protein, human
  • Calcium Channels
  • Membrane Glycoproteins
  • Peptide Fragments
  • Receptors, Cell Surface
  • SOD1 protein, human
  • SORCS1 protein, human
  • amyloid beta-protein (1-40)
  • amyloid beta-protein (1-42)
  • DNA
  • Superoxide Dismutase
  • Superoxide Dismutase-1