Scientific Reports (Jun 2024)

In vivo brain estrogen receptor density by neuroendocrine aging and relationships with cognition and symptomatology

  • Lisa Mosconi,
  • Matilde Nerattini,
  • Dawn C. Matthews,
  • Steven Jett,
  • Caroline Andy,
  • Schantel Williams,
  • Camila Boneu Yepez,
  • Camila Zarate,
  • Caroline Carlton,
  • Francesca Fauci,
  • Trisha Ajila,
  • Silky Pahlajani,
  • Randolph Andrews,
  • Alberto Pupi,
  • Douglas Ballon,
  • James Kelly,
  • Joseph R. Osborne,
  • Sadek Nehmeh,
  • Matthew Fink,
  • Valentina Berti,
  • Jonathan P. Dyke,
  • Roberta Diaz Brinton

DOI
https://doi.org/10.1038/s41598-024-62820-7
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 15

Abstract

Read online

Abstract 17β-estradiol, the most biologically active estrogen, exerts wide-ranging effects in brain through its action on estrogen receptors (ERs), influencing higher-order cognitive function and neurobiological aging. However, our knowledge of ER expression and regulation by neuroendocrine aging in the living human brain is limited. This in vivo brain 18F-fluoroestradiol (18F-FES) Positron Emission Tomography (PET) study of healthy midlife women reveals progressively higher ER density over the menopause transition in estrogen-regulated networks. Effects were independent of age, plasma estradiol and sex hormone binding globulin, and were highly consistent, correctly classifying all women as being postmenopausal or premenopausal. Higher ER density in target regions was associated with poorer memory performance for both postmenopausal and perimenopausal groups, and predicted presence of self-reported mood and cognitive symptoms after menopause. These findings provide novel insights on brain ER density modulation by female neuroendocrine aging, with clinical implications for women’s health.