Estrogen receptor-beta variants are associated with increased risk of Alzheimer's disease in women with Down syndrome

Qi Zhao, Joseph H. Lee, Deborah Pang, Alexis Temkin, Naeun Park, Sarah C. Janicki, Warren B. Zigman, Wayne Silverman, Benjamin Tycko, Nicole Schupf

Research output: Contribution to journalArticle

Abstract

Background/Aims: Genetic variants that affect estrogen activity may influence the risk of Alzheimer's disease (AD). We examined the relation of polymorphisms in the gene for the estrogen receptor-beta (ESR2) to the risk of AD in women with Down syndrome. Methods: Two hundred and forty-nine women with Down syndrome, 31-70 years of age and nondemented at baseline, were followed at 14- to 18-month intervals for 4 years. Women were genotyped for 13 single-nucleotide polymorphisms (SNPs) in the ESR2 gene, and their association with AD incidence was examined. Results: Among postmenopausal women, we found a 2-fold increase in the risk of AD for women carrying 1 or 2 copies of the minor allele at 3 SNPs in introns seven (rs17766755) and six (rs4365213 and rs12435857) and 1 SNP in intron eight (rs4986938) of ESR2. Conclusion: These findings support a role for estrogen and its major brain receptors in modulating susceptibility to AD in women.

Original languageEnglish (US)
Pages (from-to)241-249
Number of pages9
JournalDementia and Geriatric Cognitive Disorders
Volume32
Issue number4
DOIs
StatePublished - Feb 1 2012

Keywords

  • Alzheimer's disease
  • Down syndrome
  • Estrogen
  • Estrogen receptor-beta

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Cognitive Neuroscience
  • Psychiatry and Mental health

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    Zhao, Q., Lee, J. H., Pang, D., Temkin, A., Park, N., Janicki, S. C., Zigman, W. B., Silverman, W., Tycko, B., & Schupf, N. (2012). Estrogen receptor-beta variants are associated with increased risk of Alzheimer's disease in women with Down syndrome. Dementia and Geriatric Cognitive Disorders, 32(4), 241-249. https://doi.org/10.1159/000334522