Why do more women than men get Alzheimer’s disease? In their quest to find the answer, neuroscientist Roberta Diaz Brinton, PhD, and her colleagues in the Center for Innovation in Brain Science at the University of Arizona Health Sciences, have been awarded a $10.3 million five-year Program Project Grant (PPG) from the National Institute on Aging at the National Institutes of Health.

The number of women affected by this neurodegenerative brain disease that steals the mind is staggering. Of the more than 5 million Americans of all ages who have Alzheimer’s disease in 2016, more than 3 million are women. By age 65, women have a 1 in 6 chance of developing Alzheimer’s, compared to a 1 in 11 chance for men. Women in their 60s are twice as likely to develop Alzheimer’s than to develop breast cancer.

Alzheimer’s also is deadly. It is the fifth-leading cause of death, according to the U.S. Centers for Disease Control and Prevention. And it is the only disease among the top 10 causes of death in America that cannot be prevented, cured or even slowed, notes the Alzheimer’s Association.

That is why Dr. Brinton is passionate about pursuing a medical breakthrough.

“The greatest risk factors for Alzheimer’s are age, the female sex and genetics, specifically the APOE4 gene,” said Dr. Brinton, inaugural director of the UA Center for Innovation in Brain Science, who has been researching Alzheimer’s disease for more than 20 years. “Women constitute more than 60 percent of those with Alzheimer’s disease, and more than 50 percent of persons with Alzheimer’s are positive for the APOE4 gene. If positive for a single copy of the APOE4 gene, women are at greater risk than men who have two copies of the APOE4 gene.

“Our ‘Perimenopause in Brain Aging and Alzheimer’s Disease’ Program Project will build on our discovery of the biological transformations in the brain that occur during perimenopause, a neuroendocrine transition unique to women. These transformations can lead to  changes that can put the brain at risk for Alzheimer’s disease. Our goals are to discover the mechanisms underlying the heightened risk of Alzheimer’s in APOE4-positive females, and to translate these discoveries into strategies and therapeutics to a alleviate a  women’s risk of developing Alzheimer’s disease,” said Dr. Brinton, UA professor of pharmacology and neurology.

“Alzheimer’s is a devastating disease that impacts everyone, from the patient to the families who care for them, at great cost emotionally and financially. The incidence of Alzheimer’s is expected to nearly triple by 2050, if we don’t discover ways to prevent or cure this disease,” said Joe G.N. “Skip” Garcia, MD, UA senior vice president for health sciences, the Dr. Merlin K. DuVal Professor of Medicine and an elected member of the prestigious National Academy of Medicine. “Dr. Brinton and her team are at the cutting edge of Alzheimer’s research, the aging female brain and regenerative therapeutics. The impact of their exciting work will result in a better understanding of the risk of developing Alzheimer’s disease, the development of novel new therapies, and—potentially—a cure for women and men patients with this debilitating disease,” Dr. Garcia added.

The long duration of illness, much of it spent in a state of disability and dependence, before death contributes significantly to the public health impact of Alzheimer’s, one of the costliest chronic diseases. And while women have a greater chance of developing Alzheimer’s disease than men, they also more often are responsible for caring for someone with Alzheimer’s.

Alzheimer’s by the Numbers

In Arizona, about 130,000 individuals age 65 and older are living with Alzheimer’s in 2016, according to the Alzheimer’s Association—nearly 2 percent of the population. Arizona is one of only three states expected to have an increase of more than 50 percent by 2050—to 200,000.

Older Hispanics are about one and one-half times as likely to have Alzheimer’s and other dementias, and older African-Americans about twice as likely, as older whites. Genetic factors do not appear to account for the difference; instead, cardiovascular disease and diabetes, which are associated with an increased risk for Alzheimer’s disease and other dementias, are believed to account for the difference as the conditions are more prevalent in African Americans and Hispanics.

Collaborating to Find a Cure

Among the most highly competitive, scientifically peer-reviewed funding mechanisms awarded by the NIH, Program Project Grants (PPGs) fund collaborative research programs in differing areas of expertise to achieve results not attainable by investigators working independently. Better treatments and eventually a cure for Alzheimer’s will take the work of scientists in many fields. Joining Dr. Brinton on the UAHS PPG will be researchers at the UA and University of Southern California researchers Arthur Toga, PhD, and Paul Thompson, PhD, neuroimaging and informatics; Enrique Cadenas, MD, PhD, pharmacology; Christian Pike, PhD, gerontology; and Meng Law, MD, neuroradiology.

The program project, “Perimenopause in Brain Aging and Alzheimer’s Disease,” is supported by the National Institute on Aging of the National Institutes of Health under award number 2P01AG026572-11.