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Among men, androgens are associated with a decrease in Alzheimer's disease risk.

Cynthia D J Kusters1, Kimberly C Paul2, Tahmineh Romero3

  • 1Department of Human Genetics, David Geffen School of Medicine, Los Angeles, California, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|March 20, 2023
PubMed
Summary
This summary is machine-generated.

Higher androgen levels in men are linked to a reduced risk of Alzheimer's disease (AD). This study suggests androgens may be neuroprotective for men, potentially delaying AD diagnosis.

Keywords:
Alzheimer's diseaseMendelian randomizationandrogensepidemiologygeneticssex hormonessex stratified

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Area of Science:

  • Neuroendocrinology
  • Genetics
  • Alzheimer's Disease Research

Background:

  • Sex hormones are hypothesized to influence Alzheimer's disease (AD) risk.
  • Previous research suggests a potential protective role for certain sex hormones against AD.

Purpose of the Study:

  • To investigate the causal relationship between sex steroid hormones and Alzheimer's disease (AD) risk.
  • To assess the association between genetically determined hormone levels and AD using a Mendelian randomization (MR) approach.

Main Methods:

  • Utilized Mendelian randomization (MR) analysis with inverse-variance weighting (IVW).
  • Employed summary statistics from genome-wide association studies (GWAS).
  • Included independent genetic variants with stringent significance thresholds (p < 5x10⁻⁸) and low linkage disequilibrium (R² < 0.001).

Main Results:

  • In men, increased androgen levels (testosterone, dehydroepiandrosterone sulfate [DHEAS], androsterone sulfate) were significantly associated with a decreased risk of AD.
  • No significant association was found between sex steroid hormones and AD risk in women.
  • Analysis for estradiol in women had limited statistical power.

Conclusions:

  • Higher concentrations of androgens are associated with a reduced risk of AD in men.
  • Androgens may possess neuroprotective properties in men, potentially preventing or delaying AD onset.
  • The findings suggest a potential causal link between androgens and AD risk specifically in men.