TUCSON, Ariz. – Why do more women than men get Alzheimer's disease? In their quest to find the answer, neuroscientist Roberta Diaz Brinton, PhD, and her collegues 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 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.
(For more information: 2016 Alzheimer's Disease Facts and Figures, https://www.alz.org/documents_custom/2016-facts-and-figures.pdf)
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.
Alzheimer's Association Sex and Gender in Alzheimer's (SAGA) Research Grant Award
Further expanding the impact of Alzheimer's disease research and innovation at the UA, in September Dr. Brinton was awarded one of the first-ever Alzheimer's Association Sex and Gender in Alzheimer's (SAGA) research grant awards. The three-year $249,000 grant will fund the study, "Sex Differences in the ApoE4 Brain: Accelerated Myelin Catabolism for Fuel." Dr. Brinton will investigate how the risk factor gene, APOE4, impacts development of Alzheimer's pathology in both females and males. Further, she will test the efficacy of the regenerative therapeutic allopregnanolone to prevent the loss of myelin, a fatty material that insulates the nerve fibers and increases the speed of electrical impulses needed for brain cell communication. The breakdown of myelin has been implicated in the disruption of brain signaling in Alzheimer's.
About Dr. Brinton
Dr. Brinton joined the UA Health Sciences in May 2016 from the University of Southern California. As director of the UA Center for Innovation in Brain Science and professor of pharmacology and neurology, she is accelerating the UA's innovations in brain science to "bring the power of precision medicine to personalize therapeutics to cure neurological disease." She has been principal investigator for major National Institutes of Health-funded program project and center grants focused on brain disorders, and her research has been continuously funded by NIH for more than 20 years. For more information about Dr. Brinton, visit http://uahs.arizona.edu/leadership-team/roberta-diaz-brinton-phd
About the UA Center for Innovation in Brain Science
Established in 2016, the UA Center for Innovation in Brain Science will accelerate the advancement of evidence-based clinical care of brain disorders caused by disease, genetics or trauma. In the 21st century, there is not a single cure for a single neurodegenerative disease. The mission of the Center for Innovation in Brain Science is to create breakthrough therapeutics for neurodegenerative diseases that affect Arizonans, the nation and beyond. The Center will serve as a knowledge, resource and community hub for the clinical to translational to basic science neuroscience community across the UA and Banner – University Medical Center. For brain innovation teams, the Center will provide enabling expertise and infrastructure to develop therapeutics for neurodegenerative diseases. Through the UA Center for Innovation in Brain Science, the vision of Precision Medicine Through Precision Discovery for Personalized Therapeutics to Cure Neurological Disease…will become reality. For more information: http://cibs.uahs.arizona.edu
About the University of Arizona Health Sciences
The University of Arizona Health Sciences is the statewide leader in biomedical research and health professions training. The UA Health Sciences includes the UA Colleges of Medicine (Phoenix and Tucson), Nursing, Pharmacy and Mel and Enid Zuckerman College of Public Health, with main campus locations in Tucson and the growing Phoenix Biomedical Campus in downtown Phoenix. From these vantage points, the UA Health Sciences reaches across the state of Arizona and the greater Southwest to provide cutting-edge health education, research, patient care and community outreach services. A major economic engine, the UA Health Sciences employs almost 5,000 people, has nearly 1,000 faculty members and garners more than $126 million in research grants and contracts annually. For more information: http://uahs.arizona.edu
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