Ovariectomy and 17β-estradiol modulate the levels of Alzheimer's amyloid β peptides in brain

S. S. Petanceska, V. Nagy, D. Frail, S. Gandy

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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of aggregated forms of the 40- and 42-amino acid Aβ peptides (Aβ40 and Aβ42). Estrogen replacement therapy (ERT) in postmenopausal women is associated with decreased risk for AD and/or delay in disease onset. The mechanism by which estrogen exerts this neuroprotective effect is elusive. 17β-estradiol (E2) was shown to reduce the release of Aβ peptides by primary neuronal cultures of murine and human origin. To test whether estrogen can modulate the metabolism of Aβ peptides in vivo, four experimental sets of guinea pigs were used: intact animals, ovariectomized animals, and ovariectomized animals that received E2 at two different doses. Ovariectomy was associated with a 1.5-fold average increase in total brain Aβ levels as compared to intact controls. E2 treatment significantly reversed the ovariectomy-induced increase in brain Aβ levels. The high-dose E2 treatment did not lead to further decrease in brain Aβ beyond the one observed with the low-dose E2 treatment. Our results infer that cessation of ovarian estrogen production in postmenopausal women might facilitate Aβ deposition by increasing the local concentrations of Aβ40 and Aβ42 peptides in brain and suggest that modulation of Aβ metabolism may be one of the ways by which ERT prevents and/or delays the onset of AD in postmenopausal women. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)1317-1325
Number of pages9
JournalExperimental Gerontology
Issue number9-10
StatePublished - 2000
Externally publishedYes


  • 17β-Estradiol
  • Amyloid β
  • Animal model
  • Estrogen replacement therapy
  • Guinea pigs


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