Alzheimer’s disease hits women harder than men. Nearly two-thirds of Americans who have Alzheimer’s are women, according to the Alzheimer’s Association. Worldwide, 47 million people are living with Alzheimer’s and other dementias — including nearly 6 million in the United States — so the number of women affected is staggering.

The neurodegenerative disorder’s most common form, called late-onset Alzheimer’s disease, occurs after age 65.

“We know Alzheimer’s disease can start 10 to 20 years before diagnosis,” said Roberta Diaz Brinton, a leading expert in Alzheimer’s disease biology and therapeutic development and inaugural director of the Center for Innovation in Brain Science at the University of Arizona Health Sciences.

“Further, we know that there is a sex difference in the prevalence of the disease. Curing the disease requires that we discover the earliest events in the brain in both women and men that lead to emergence of disease symptoms later in life.”

Recently, the National Institute on Aging, part of the National Institutes of Health, awarded Brinton a five-year, $5.9 million grant to do exactly that. The goal of the project is to identify the sex-specific mechanisms driving Alzheimer’s disease and to translate the discoveries into novel therapeutics to prevent, delay and potentially reverse its course in women and men. Currently, no treatments exist to stop or reverse Alzheimer’s.

As Alzheimer's disease progresses, women with the disease exhibit a broader range of dementia-related behaviors and greater cognitive decline than men. Studies have found evidence that women’s brains are more vulnerable to Alzheimer’s than men’s, but the reasons are unknown. Brinton’s study aims to define the biochemical pathways that lead to sex differences in the disease.

“Outcomes of our research will generate therapeutic targets for precision medicine interventions for both women and men during the early stage of Alzheimer’s, when the potential to prevent, delay and reverse disease progression is greatest,” Brinton said.

Brinton has assembled a research team with expertise spanning brain imaging, mitochondrial bioenergetics, molecular genetics, sex differences and computational systems biology.

Brinton will serve as the team’s primary director. Brain imaging will be led by Lisa Mosconi, associate director of the Alzheimer’s Prevention Clinic and associate professor of neuroscience in neurology at Weill Cornell Medicine. The bioenergetic analyses will be led by Fei Yin, assistant professor in the UA Department of Pharmacology and associate director of the Center for Innovation in Brain Science. Computational systems biology will be led by Rui Chang, associate professor with the UA Department of Neurology and associate director of computational systems biology at the Center for Innovation in Brain Science.

“Dr. Brinton’s vision and determination has attracted a multitalented team of researchers who are working together to discover the keys to understanding the role of gender in the development and progression of Alzheimer’s disease,” said UA President Robert C. Robbins. “As the average lifespan continues to increase, improving health, happiness and quality of life is crucial, and the UA’s new strategic plan prioritizes global leadership in precision medicine that could prevent and potentially reverse the course of this deadly disease.”

The study, “Sex Differences in the Molecular Determinants of Alzheimer’s Disease Risk: Prodromal Endophenotype,” is supported by the National Institute on Aging of the National Institutes of Health under award No. R01-AG057931. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Brinton and Chang also serve as co-principal investigators on a collaborative effort to identify metabolic dysfunction in Alzheimer’s in a study with Duke University funded under National Institute on Aging grant No. RF1-AG059093.

A version of this article originally appeared on the UA Health Sciences website: https://opa.uahs.arizona.edu/newsroom/news/2019/why-women-studying-role-gender-alzheimers-disease