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


Year of Publication:
Contact PI Name:
Pattie S. Green
Contact PI Affiliation:
Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington, USA
Kelly Bales, Steven Paul, Guojun Bu
Primary Reference (PubMED ID):
Funding Source:
Alzheimer's Association
National Institutes of Health (NIH)
Study Goal and Principal Findings:

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. This study 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 and 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 APP 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. These 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. 

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Biologic - Hormone
Therapeutic Agent:
Therapeutic Target:
Estrogen Receptor

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest


Outcome Measured
Outcome Parameters
Brain-beta Amyloid Peptide-Total
Brain-Buffer Insoluble beta Amyloid Peptide 40
Brain-Buffer Insoluble beta Amyloid Peptide 42
Brain-Buffer Soluble beta Amyloid Peptide 40
Brain-Buffer Soluble beta Amyloid Peptide 42
Soluble Amyloid Precursor Protein alpha (sAPP alpha)
Soluble Amyloid Precursor Protein beta (sAPP beta)
Amyloid Precursor Protein (APP)
Brain-beta Amyloid Deposits
Drug Concentration-Plasma
Organ Weight