Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families

Karen T. Cuenco, Robert Friedland, Clinton T. Baldwin, Jianping Guo, Badri Vardarajan, Kathryn L. Lunetta, L. Adrienne Cupples, Robert C. Green, Charles DeCarli, L. A. Farrer Lindsay A.

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

In vitro and animal model studies suggest that transthyretin (TTR) inhibits the production of the amyloid β protein, a major contributor to Alzheimer disease (AD) pathogenesis. We evaluated the association of 16 TTR single nucleotide polymorphisms (SNPs) with AD risk in 158 African American and 469 Caucasian discordant sibships from the MIRAGE Study. There was no evidence for association of TTR with AD in either population sample. To examine the possibility that TTR SNPs affect specific components of the AD process, we tested association of these SNPs with four measures of neurodegeneration and cerebrovascular disease defined by magnetic resonance imaging (MRI) in a subset of 48 African American and 265 Caucasian sibships. Five of seven common SNPs and several haplotypes were significantly associated with hippocampal atrophy in the Caucasian sample. Two of these SNPs also showed marginal evidence for association in the African American sample. Results for the other MRI traits were unremarkable. This study highlights the potential value of neuroimaging endophenotypes as a tool for finding genes influencing AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)249-256
Number of pages8
JournalNeurobiology of Aging
Volume32
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • Alzheimer disease
  • Genetic association
  • Hippocampal atrophy
  • Magnetic resonance imaging
  • Transthyretin

ASJC Scopus subject areas

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

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  • Cite this

    Cuenco, K. T., Friedland, R., Baldwin, C. T., Guo, J., Vardarajan, B., Lunetta, K. L., Cupples, L. A., Green, R. C., DeCarli, C., & Farrer Lindsay A., L. A. (2011). Association of TTR polymorphisms with hippocampal atrophy in Alzheimer disease families. Neurobiology of Aging, 32(2), 249-256. https://doi.org/10.1016/j.neurobiolaging.2009.02.014