Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease

Pattie S. Green, Kelly Bales, Steven Paul, Guojun D Bu

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Epidemiological studies implicate estrogen deprivation as a risk factor for Alzheimer's disease and postmenopausal estrogen replacement as protective factor. One potential mechanism involves estrogen attenuation of β-amyloid (Aβ) peptide accumulation. We examined the effect of estrogen on amyloid accumulation in female PDAPP mice, which express human amyloid precursor protein (APP) with the V717F mutation. These animals deposit Aβ 1-42 in the hippocampus and neocortex amd develop Alzheimer-like neuropathology. Mice were subjected to ovariectomy, ovariectomy with estrogen replacement, or sham surgery at 3 months of age, and levels of cerebral Aβ 1-40 and 1-42 were determined after 5 months of treatment. Neither estrogen deprivation nor estrogen replacement altered Aβ accumulation in the hippocampus or neocortex. Similarly, immunoreactivity for full-length human APP and secreted APPα was unchanged. Estrogen status of the animals was confirmed using a variety of techniques, including uterine and pituitary weight, vaginal cytology, and plasma estradiol concentrations. There was no correlation between plasma estradiol levels and accumulation of either Aβ 1-40 or Aβ 1-42 in the brain. Our observations indicate that long-term estrogen therapy does not alter amyloid pathology in PDAPP mice, an animal model of Alzheimer's disease, and question the role of estrogen in Aβ deposition in brain.

Original languageEnglish (US)
Pages (from-to)2774-2781
Number of pages8
JournalEndocrinology
Volume146
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

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Amyloid
Alzheimer Disease
Estrogens
Estrogen Replacement Therapy
Amyloid beta-Protein Precursor
Neocortex
Ovariectomy
Therapeutics
Estradiol
Hippocampus
Brain
Cell Biology
Epidemiologic Studies
Animal Models
Pathology
Weights and Measures
Peptides
Mutation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease. / Green, Pattie S.; Bales, Kelly; Paul, Steven; Bu, Guojun D.

In: Endocrinology, Vol. 146, No. 6, 06.2005, p. 2774-2781.

Research output: Contribution to journalArticle

Green, Pattie S. ; Bales, Kelly ; Paul, Steven ; Bu, Guojun D. / Estrogen therapy fails to alter amyloid deposition in the PDAPP model of Alzheimer's disease. In: Endocrinology. 2005 ; Vol. 146, No. 6. pp. 2774-2781.
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