Estrogen-like Compound May Reduce Risk for Alzheimer's in Mice

Newswise — New research accepted for publication in the journal Endocrinology reveals that mice with induced Alzheimer's-like symptoms had improved cognitive function when given the synthetic estrogen-like hormone propylpyrazole triol (PPT).

"This synthetic hormone improved behavior much the way that estrogen does," said study leader Dr. Christian Pike, associate professor at the University of Southern California's School of Gerontology. But unlike estrogen, which enlarges the uterus and is a known risk factor for endometrial and breast cancer, PPT caused no obvious changes to the animals' reproductive tract.

"This may be a promising strategy to maximize hormone therapy benefits and minimize its risk," said Pike.

Estrogen-based hormone therapy has long been studied as a therapeutic option for postmenopausal women to reduce the risk of several age-related disorders, including osteoporosis and Alzheimer's disease. Some studies have suggested that estrogen may lower the risk of Alzheimer's. This hormone, however, has also been associated with a number of adverse health effects.

A potential alternative approach to estrogen-based hormone therapy is a synthetic form of the hormone known as selective estrogen receptor modulators (SERMs). SERMs can have the same effect as estrogen, but specifically target certain tissues and certain parts of the body. Two recently developed SERMs—PPT and diarylpropionitrile (DPN)—have been shown to protect cultured neurons from damage.

For their study, the researchers examined the effects of estrogen, PPT, and DPN on female mice. The data confirmed previous studies showing that estrogen significantly reduced the buildup in the brain of the protein beta amyloid, which has been implicated in the development of Alzheimer's disease. Estrogen also reduced cognitive decline in the mice.

The researchers also observed that PPT was effective in lowering beta amyloid accumulation in most brain regions and also lessened working memory deficits. PPT also appeared to have no adverse impact on the animals' reproductive tracts.

DPN did not demonstrate the same protective effects.

"These findings suggest it may be possible to design an optimal compound that offers the best protection with the least risk," said Pike. "This study also should encourage further animal and human research on the potential benefits of SERMs."

The study was funded by the National Institute on Aging.

The other author of the study was USC graduate student Jenna Carroll.

The paper "Selective estrogen receptor modulator differentially regulate Alzheimer-like changes in female 3xTg-AD mice" will appear in the May 2008 issue of Endocrinology, a publication of The Endocrine Society.

Founded in 1916, The Endocrine Society is the world's oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society's membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at

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