Accelerated Cell Aging in Female APOE-e4 Carriers

Implications for Hormone Therapy Use

This study examines change in leukocyte telomere length (TL) in post-menopausal women who are carriers of the apolipoprotein-e4 (APOE-e4) risk allele or are non-carrier controls. The impact of hormone replacement therapy (HT) on telomere shortening was also analyzed.

This study reveals that carriers of the APOE-e4 risk allele (a major genetic risk factor for cognitive decline, Alzheimer’s disease, and early mortality), may benefit from HT.

This investigation included 63 high-functioning, post-menopausal women: 24 APOE-e4 carriers and 39 non-carrier controls. Thirty-one participants were randomized to go off HT and 32 remained on HT for the two-year study duration. Using a longitudinal, randomized design, the authors tested whether carriers of the APOE-e4 allele exhibited accelerated cell aging (shortened TL), and whether HT buffers against TL decline.

Key Findings:

  • Logistic regression analyses (adjusting for age, education, HT group, and baseline TL) revealed that the odds of TL shortening were more than six times higher for APOE-e4 carriers compared to non-carriers over the two-year period.
  • APOE-e4 carriers who went off their HT regimen showed telomere attrition, while APOE-e4 carriers who remained on HT showed little to no TL decline.

The sample size of this study was small, however the findings demonstrate that over just a two-year period, HT may buffer against TL attrition in women at risk of cognitive decline.