Twelve senior USC researchers are joining forces to prevent or delay the onset of Alzheimer’s disease in women, who currently make up 68 percent of the victims of this brain-destroying epidemic sweeping the nation.

The project, led by primary investigator Roberta Diaz Brinton, professor at the USC School of Pharmacy, will examine disparities between clinical findings that hormone therapy increases a woman’s risk of Alzheimer’s disease in contrast to basic science outcomes and clinical observations that estrogen and progesterone therapies promote neurological health and prevent Alzheimer’s disease.

“Our approach for this project is unique,” Brinton said. “We have joined an interdisciplinary basic science team at USC with an external board of clinical scientists specializing in women’s health, from USC, UC San Francisco and the National Institutes of Health. This board worked with us to design a study to generate critical basic science knowledge directly leading to clinically relevant therapies.”

The project hypothesizes that progesterone actually reduces a woman’s vulnerability to neurodegenerative diseases such as Alzheimer’s disease. To prove this, the scientists will investigate progesterone action at seven levels of functioning in the brain from the molecular to the behavioral to actual Alzheimer’s disease pathology.

“Our ultimate goal is to identify the conditions in the female brain that benefit from hormone therapy and those conditions that lead to adverse outcomes,” Brinton explained. “So far, the answers to these questions are ambiguous, leaving an unclear path for women and their physicians.”

Seven different USC laboratories will conduct the research involving Brinton, Jon Nilsen, JunMing Wang, Enrique Cadenas and Nouri Neamati of the USC School of Pharmacy; Caleb Finch, Todd Morgan and Christian Pike of the USC Leonard Davis School of Gerontology; Wendy Mack and Paul Marjoram of the Keck School of Medicine of USC; and Richard Thompson, Michel Baudry and Michael Foy of USC College.

The School of Pharmacy is the lead on the five-year, $8 milllion project grant awarded by the National Institute on Aging at the NIH.

One example of the synergy is that team members at the School of Gerontology will develop unique rodent models mirroring human perimenopause and menopause while the lab at USC College will unravel the impact of progestins on memory.

Meanwhile, the Keck School of Medicine group will oversee the data management, integrating outcomes across all units, and the School of Pharmacy investigators will explore progestin regulation of neural stem cells and harness the findings from across the program to develop optimal hormone brain therapies.

“There is an urgent need for the results of our research,” Brinton said. “The baby boomers are aging, and the nation faces the prospect of tens of millions of women in long-term neurodegenerative states. And we don’t have the basic science knowledge to answer the clinical question: Does hormone therapy prevent or increase the risk of Alzheimer’s disease? That’s the question we are determined to definitively answer.”