$4M NIH Grant Awarded for Dementia Research

Scientists will study how menopause impacts dementia and test potential new drug

Research scientists at Albany Medical College have been awarded a $4 million, five-year grant from the National Institutes of Health (NIH) to study the effects of menopause on Alzheimer’s disease and other dementias, and to test an estrogen therapy for dementia.

Production of the hormone estrogen decreases during menopause. Low estrogen levels are associated with an increased risk for Alzheimer’s disease, vascular disease, and cognitive decline. It is also known that the earlier menopause begins, the higher a woman’s risk of developing dementia. Further, current FDA-approved treatments for Alzheimer’s that target amyloid proteins in the brain have been reported to be 29 percent less effective in women.

“Menopausal women may be a uniquely vulnerable population who could benefit most from new preventative therapies,” said Kristen Zuloaga, PhD, associate professor in the Department of Neuroscience and Experimental Therapeutics, who is leading the study.

November is Alzheimer’s Disease Awareness Month.

Dr. Zuloaga and her team will test the effects of perimenopause, menopause, and a brain-specific estradiol prodrug – that is, an estrogen therapy that metabolizes when it reaches the brain – on mouse models of Alzheimer’s disease and multiple etiology dementia (when someone has more than one type of dementia).

“Our previous studies showed that menopause causes weight gain and glucose intolerance and exacerbates symptoms in vascular contributions to cognitive impairment and dementia,” said Dr. Zuloaga. “In this study, we’re narrowing our focus to test whether increasing estrogen signaling in the brain can help protect against dementia. We also hope to identify the common underlying cellular mechanisms of dementia.”

Dr. Zuloaga and her team will collaborate with colleagues from the Departments of Molecular and Cellular Physiology and Regenerative and Cancer Cell Biology, as well as scientists at the Neural Stem Cell Institute, who will assist with study design, perform bioinformatics analysis on vascular gene changes, and conduct studies in stem cell-derived endothelial cells to assess the protective effects of the prodrug used in the mouse studies.

Supporting the continuation of an NIH-funded study that began in 2019, this grant was awarded in recognition of the continuing importance of Dr. Zuloaga’s work and the impactful papers that resulted from her previous studies. Titled, “Metabolic and Hormonal Mechanisms of VCID,” the study is funded by the NIH’s National Institute of Neurological Disorders and Stroke.