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Estrogen treatment improves spatial learning in APP + PS1 mice but does not affect beta amyloid accumulation and plaque formation


Year of Publication:
Contact PI Name:
Jukka Puolivali
Contact PI Affiliation:
Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland
T. Heikkinen, G. Kalesnykas, A. Rissanen, T. Tapiola, S. Iivonen, J. Wang, J. Chaudhuri, H. Tanila, R. Miettinen
Primary Reference (PubMED ID):
Funding Source:
National Technology Agency of Finland
Hormos Medical Ltd. Finland
Academy of Finland
EVO Grant of the Kuopio University Hospital
Finnish Cultural Foundation
Farmos Research and Science Foundation
Kuopio University Foundation
Alfred Kordelin Foundation Finland
Study Goal and Principal Findings:

This study investigated the effects of ovariectomy (OVX) and 17β-estradiol (0.18 mg per pellet) treatment on spatial learning and memory, hippocampal beta amyloid (Aβ) levels, and amyloid plaque counts in double transgenic mice (A/P) carrying mutated amyloid precursor protein (APPswe) and presenilin-1 (PS1-A246E). After OVX at 3 months of age, the mice received estrogen treatment for the last 3 months of their lifetime before they were killed at 6, 9, or 12 months of age. Estrogen treatment in A/P OVX mice increased the number of correct choices in a position discrimination task in the T-maze, and slightly improved their performance in a win-stay task (1/8 arms baited) in the radial arm maze (RAM). However, estrogen treatment did not reverse the Aβ-dependent cognitive deficits of A/P mice in the water maze (WM) spatial navigation task. Furthermore, ovariectomy or estrogen treatment in OVX and sham-operated A/P mice had no effect on hippocampal amyloid accumulation. These results show that the estrogen treatment in a transgenic mouse model of Alzheimer’s disease (AD) improves performance in the same learning and memory tasks as in the normal C57BL/6J mice. However, the estrogen effects in these mice appeared to be unrelated to Aβ-induced cognitive deficits. These results do not support the idea that estrogen treatment decreases the risk or alleviates the symptoms of Alzheimer’s disease by inhibiting the accumulation of Aβ or formation of amyloid plaques.

Therapeutic Agent

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

Animal Model

Model Information:
Model Type:
Strain/Genetic Background:
Not Reported

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
Morris Water Maze
T Maze
Radial Arm Water Maze
Brain-beta Amyloid Peptide 40
Brain-beta Amyloid Peptide 42
beta Amyloid Deposits
Organ Weight