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SERMs May Offer Lower-Risk Alzheimer's Protection

Postmenopausal-like mouse model shows brain benefits from selective estrogen receptor modulators

THURSDAY, Feb. 14 (HealthDay News) -- Selective estrogen receptor modulators (SERMs) may offer a therapy that protects postmenopausal women from Alzheimer's disease without raising the risk of adverse effects such as breast and uterine cancer, according to the results of a mouse study published online Feb. 14 in Endocrinology.

Jenna C. Carroll and Christian J. Pike, Ph.D., of the University of Southern California in Los Angeles, used female mice to test the effects of propylpyrazole triol (PPT) and diarylpropionitrile (DPN), compared to 17β-estradiol (E2) on β-amyloid protein accumulation and hippocampal-dependent memory performance. Mice were ovariectomized (or given a sham procedure) and implanted with a pellet of one of these substances or a control for three months.

The resulting hormone depletion increased β-amyloid and decreased specific behavioral performance, but E2 inhibited these changes. PPT decreased β-amyloid in the hippocampus, subiculum and amygdala in line with E2, but did less well in the frontal cortex. DPN was ineffective in the hippocampus and subiculum, somewhat effective in the frontal cortex, and nearly as good as E2 in the amygdala. Only PPT was similar to E2 in improving the animals' behavioral performance.

"Development of SERMs that exert beneficial effects on the brain, bone and/or cardiovascular system but minimal effects on estrogen-responsive, tumor susceptible tissue is of critical importance," the authors conclude. "Our data confirm the potential of SERMs in protecting against Alzheimer's disease neuropathology and support the continued development and investigation of neuroactive SERMs as an alternative strategy to hormone therapy in preventing and perhaps treating age-related neurodegenerative disorders."

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