OHSU Center for Women’s Health Circle of Giving 2020 awardee

Obesity and Alzheimer’s Disease

Martin J. Kelly, Ph.D., and Oline K. Ronnekleiv, Ph.D.

Department of Chemical Physiology and Biochemistry, OHSU School of Medicine

By the year 2050, it is estimated that nearly 14 million Americans will be diagnosed with Alzheimer’s disease, the majority being post-menopausal women. While the reasons for increased risk in women are still unknown, some studies have shown a link between the disease and lower levels of the female hormone, estrogen.

While hormone replacement therapies can be effective in protecting women against Alzheimer’s disease, they are also associated with increased risk of cancer or blot clots.

Alternatively, members of the Kelly and Ronnekleiv labs, within the OHSU Department of chemical physiology and biochemistry, have developed an estrogenic compound, known as STX, that targets the brain but doesn’t cause side effects in other body systems. Their studies have shown that STX also protects against toxic amyloid proteins that are linked with Alzheimer’s disease.

With Circle of Giving funding, the researchers will test whether STX protects the function of “Kisspeptin” neurons in the brain, that regulate things including appetite and metabolism. This is important because obesity and type-2 diabetes (insulin resistance) in older women are linked to increased risk of Alzheimer’s disease. The study will help to define if a dysfunction in Kisspeptin neurons worsens Alzheimer’s disease, and will also lay the foundation for advancing STX to clinical trials for estrogen-dependent breast cancers.