On June 1, In recognition of National Brain Health Awareness Month, the Women’s Alzheimer’s Movement (WAM) at Cleveland Clinic announced the recipients of the 2021 WAM Research Grants, seed funding for innovative women-based Alzheimer’s research studies that will be conducted over two years, 2022-2023. Each of the five funded projects is aimed at supporting WAM’s mission, which is to help answer the question of why two out of three cases of Alzheimer’s are women, and why communities of color are especially hard hit by this fatal disease.

With these latest grants, WAM will have funded $4.25 million for 40 studies at 17 leading institutions, and positioned its grantees to earn an additional $83 million more in government and foundation funding.

“Medical research has historically left women out of clinical trials and major brain-health studies,” said Maria Shriver, founder of The Women’s Alzheimer’s Movement and Strategic Partner on Women’s Health and Alzheimer’s to Cleveland Clinic. “Getting to understand why women are at the center of this disease is why WAM was founded, to advance and strengthen research on the development of Alzheimer’s in women. We are proud to help support these new projects as we invest in the power of research to change the trajectory of women’s brain health and advance our knowledge of the ways in which Alzheimer’s affects women.”

The 2021 grantees are all affiliated with major medical institutions and are using their WAM seed grants to further test cutting-edge hypotheses about why women and communities of color are disproportionately impacted by Alzheimer’s. The full list of WAM grantees includes:

Grant recipient: Puja Agarwal, Ph.D.

Dr. Agarwal’s study, which is co-funded by the Alzheimer’s Association, addresses the disproportionate impact of Alzheimer’s disease on communities of color by studying how dietary choices affect the cognition of older adults from different cultures and ethnicities.

Grant recipient: Roberta Diaz Brinton, Ph.D., Center for Innovation in Brain Science Regents Professor, Pharmacology and Neurology at the College of Medicine at Tucson University of Arizona:

Dr. Brinton’s study builds on research supported by prior WAM grants that found that specific breast cancer therapies can reduce the risk of Alzheimer’s disease. Dr. Brinton has now expanded the investigation to determine the best therapies that control Type 2 Diabetes while also reducing the risk for Alzheimer’s.

Grant Recipient: Lisa Mosconi, Ph.D., Women’s Brain Health Initiative, Weill Cornell, New York:

Dr. Mosconi’s study investigates the existence of neurophysiological subtypes of menopause in order to determine whether certain areas of the brain are responsible for specific symptoms of menopause in mid-life women at risk for Alzheimer’s.

Grant Recipient: Jessica Caldwell, Ph.D., Director of the Women’s Alzheimer’s Movement Prevention Center:

This grant promotes and grows the impact of the WAM Prevention Center at Lou Ruvo Center for Brain Health at Cleveland Clinic Nevada by increasing the capacity for clinical treatments and research into women at risk for AD.

Grant Recipient: Dr. Mathew Blurton-Jones, Assistant Professor of Neurobiology and Behavior at UC Irvine; and Dr. Sunhil P. Gandhi, Associate Professor of Neurobiology and Behavior at UC Irvine

Question: Is there a sex difference in microglia—the brain’s immune cells?

Women have a significantly increased risk of developing Alzheimer’s Disease during their lifetime, and recent genetic evidence suggests that microglia—a form of neuro-immune cell, or immune cells in the brain—are key to Alzheimer’s risk and may be different in male and female brains. Last year, with funding from the WAM/UCI MIND Women’s Initiative, Drs. Mathew Blurton-Jones and Sunil Gandhi used cutting edge approaches to understand how this plays out in the brain. They engineered human skins to become stem cells and then to become microglia and introduced these human microglia into the brains of both female and male mouse models of Alzheimer’s disease. Using new technology that can visually capture the reaction of the microglia, they were able to show that the microglia placed into female brains reacted more aggressively—overreacted—to the pathology of Alzheimer’s. This suggests that the local brain environment, including the brain’s immune response, may place female brains at higher risk for Alzheimer’s. Since inflammation seems to be involved in the connection between women and Alzheimer’s and other neurological autoimmune diseases, this is an important step in understanding how. With the continuation of this partnership, this year, these investigators will further explore whether and why female microglia show a diminished response to localized brain injuries. The team also hopes to learn how the brain environment—and the presence or absence of estrogen—affects microglia, using animal models. Uncovering functional differences in microglia could help researchers develop more effective drugs to treat Alzheimer’s. UCI and WAM are excited to announce that this research has resulted in an additional $1.9 million multi-year grant from the National Institutes of Health for Drs. Blurton-Jones and Gandhi to continue their important work.

Grant Recipient: Dr. Jessica Z.K. Caldwell, Clinical Neuropsychologist at the Lou Ruvo Center at Cleveland Clinic

WAM funding over the past three years has helped Dr. Jessica Caldwell, a clinician-scientist, leap from small studies of sex differences in Alzheimer’s disease to building a substantial program of sex- and gender-based research on Alzheimer’s disease biomarkers. Dr. Caldwell’s initial WAM funding, on how sex impacts the way amyloid effects memory and hippocampus volumes, led to publications that in turn led to her joining a major grant as project lead, which led to even more data, publications, and collaborations. Dr. Caldwell’s most recent WAM grant has allowed her to hire a postdoctoral fellow to help her expand and enrich our understanding of these critical differences in Alzheimer’s. Altogether, WAM grants have led to a wide-ranging program of sex differences in Alzheimer’s disease that reaches other investigators, studies, trainees, and patients. Aside from papers and grants, WAM has played a critical role in helping her find her career calling to build research programs that can have real-world impact for women at risk for Alzheimer’s, as well as for trainees.

Grant Recipient: Elizabeth Head, Ph.D., Department of Pathology and Laboratory Medicine, University of California Irvine:

This grant studies sex differences in the neuropathology of people with Down’s syndrome, all of whom eventually develop Alzheimer’s disease. It is awarded as part of the UCI MIND WAM Women’s Research Initiative under the direction of Joshua Grill, PhD.

Grant recipient: Dr. Roberta Diaz Brinton, Director of the Center for Innovation in Brain Science, and Professor in the Departments of Pharmacology and Neurology, at the University of Arizona

For the past four years, WAM has supported Dr. Brinton’s groundbreaking work on the relationship between estrogen and Alzheimer’s disease. Dr. Brinton and her colleagues investigated the impact of breast cancer therapies on the risk of developing Alzheimer’s later in life. Outcomes of their research yielded exciting findings which are currently embargoed but will appear soon in the March 24, 2020 issue of JAMA Open Network. To ensure that the women, clinicians and scientists worldwide are informed, the results of Brinton’s WAM study will be freely available through the JAMA Open Network Neurology.