AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Transl Res 2009;1(2):131-147

Review Article
Potential role of estrogen in the pathobiology and prevention of
Alzheimer's disease

Whitney Wharton, Carey E. Gleason, Katelin R. Lorenze, Tamara S. Markgraf, Michele L. Ries, Cynthia M.
Carlsson, Sanjay Asthana

Laboratory for Cancer Ontogeny and Therapeutics, Center for Translational Cancer Research, Department of
Biological Sciences, University of Delaware, Newark, DE 19716, USA

Received January 14, 2009; accepted January, 2009; available online January, 2009

Abstract: Over a decade of converging findings from clinical, observational and basic science research indicate
that estrogen administration during the menopausal transition exerts beneficial effects on cognition and
decreases a woman’s risk of developing Alzheimer’s disease (AD) later in life. This review article stresses the
research focus of AD prevention, and introduces hormone therapy (HT) as a probable catalyst that may achieve
this goal. Furthermore, this article outlines 3 mechanisms proposed to mediate estrogen’s beneficial effects,
discusses the controversy surrounding HT administration, and presents the most promising estrogen related
research in AD prevention and treatment. Although controversial, cumulative evidence suggests that the potential
of estrogen initiated during perimenopause to prevent AD needs to be systematically evaluated. (AJTR901005).

Key Words: Estrogen, estrogen therapy, hormone therapy, cognition, Alzheimer’s disease, postmenopausal
cognition, women’s health initiative

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Address all correspondence to:
Whitney Wharton, Ph.D.
University of Wisconsin School of Medicine and Public Health
William S. Middleton VA Hospital
2500 Overlook Terrace, GRECC 11G
Madison WI 53705
Phone: (608) 256-1901, ext. 11516