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Updated: May 13, 2026
09:38
Generalized Psychophysiological Interaction (PPI) Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Estrogen receptor polymorphisms and incident dementia: the prospective 3C study
Joanne Ryan1, Isabelle Carrière2, Laure Carcaillon3
1Inserm, U1061, Neuropsychiatry: Epidemiological and Clinical Research, Montpellier, France; Université Montpellier1, Montpellier, France; Murdoch Children's Research Institute, Royal Children's Hospital, Victoria, Australia.
Summary
Genetic variations in estrogen receptors (ESR) may influence Alzheimer's disease (AD) risk, particularly in women. The ESR1rs2234693 polymorphism modifies AD risk associated with the APOE ε4 allele.
Area of Science:
- Neuroscience
- Genetics
- Epidemiology
Background:
- Genetic variations in estrogen receptors (ESR) are investigated for potential links to Alzheimer's disease (AD) incidence.
- These associations may be influenced by genetic and environmental factors, including gender and hormone use.
Purpose of the Study:
- To examine the association between estrogen receptor alpha (ESR1) and beta (ESR2) polymorphisms and dementia incidence over seven years.
- To investigate potential effect modification by gender, apolipoprotein E (APOE) ε4 allele, and hormone treatment.
Main Methods:
- Utilized data from 6959 older adults in the Three City Study.
- Employed multivariate-adjusted Cox regression models with delayed entry to analyze dementia incidence.
- Assessed five ESR1 and ESR2 polymorphisms, considering gender, APOE ε4, and hormone treatment as modifiers.
Main Results:
- In women, the ESR1rs2234693 CC genotype showed a modest increased risk for AD (aHR: 1.54).
- This genotype substantially amplified AD risk in women carrying the APOE ε4 allele (aHR: 3.24).
- A nominally significant interaction was observed between ESR1 and ESR2 polymorphisms for all dementia risk (P = .04); no significant associations were found in men.
Conclusions:
- The ESR1rs2234693 polymorphism may act as an effect modifier in women.
- This polymorphism influences the association between ESR2 and dementia risk, and AD risk related to the APOE ε4 allele.
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