Here at the Women’s Alzheimer’s Movement (WAM) at Cleveland Clinic, we fund vital gender-specific research with annual seed grants. This year, we awarded grants to three talented researchers with promising studies that could get us closer to understanding why women are twice as likely as men to develop Alzheimer’s disease and maybe even help develop better prevention and treatment strategies. We sat down with these exciting 2025 grantees and discussed what they’re working on and what they hope to learn with their WAM Grants.
WAM Young Investigator Award – Jielin Xu, PhD
My name is Dr. Jielin Xu. I am really grateful and honored to be the recipient of WAM Young Investigator Award 2025. Thank you, Maria and WAM!
I work in Dr. Feixiong Cheng’s lab at the Lerner Research Institute. My research really focuses on leveraging AI and various types of biological data to understand the heterogeneity—or diversity—and the complexities of Alzheimer’s Disease.
My research in this grant focuses on understanding why men and women experience brain inflammation differently, especially how immune cells in the brain—called microglia—respond to Alzheimer’s disease. The project has three main parts: First, we’ve built a comprehensive digital resource using data from more than 2,200 donated human brain samples (over 900 from women and 1,300 from men). These include individuals with Alzheimer’s disease and other brain diseases, as well as donors who had Alzheimer’s-related brain changes but no actual memory problems. This allows us to study disease resilience, offering insights into potential treatment strategies for Alzheimer’s disease. Second, we will develop an AI tool to uncover how microglia contribute to Alzheimer’s disease differently in men and women by analyzing both Alzheimer’s disease and resilience samples. By comparing disease and resilience profiles within each sex and across sexes, we aim to identify sex-specific disease mechanisms driven by microglia. Finally, we’ll use what we learn to suggest better, more tailored treatment options for women with Alzheimer’s disease, and we’ll check how well they work using data from a large set of real-world health records. Our goal is to understand how to identify and treat women for Alzheimer’s more effectively in the future, which will help women and men.
Established Investigator Award – Antoine Louveau, PhD
My name is Antoine Louveau. I’m an assistant professor in the neuroscience department of the Cleveland clinic, and I’m this year’s honored recipient of the established investigator WAM award. My laboratory is interested in the brain vasculature. This consists of the network of blood vessels running throughout the brain, which tightly control what comes in and out.
In Alzheimer’s disease, this system is dysregulated in ways we are still trying to figure out. In our studies, we removed a molecule from the vasculature that we believe disrupts this system in Alzheimer’s disease. To our surprise, the loss of this molecule made women in a preclinical model of Alzheimer’s better, with improved cognitive function and decreased pathology, but it had no effects in men.
The current funding will investigate how this molecule is important in females but less so in males. Particularly, we will test the interaction of our molecules with sex chromosomes to maintain the integrity of the brain vasculature in female preclinical models. We believe that this project will shine light into sex-specific aspects of Alzheimer’s disease pathologies and provide new therapeutic avenues, particularly for women. It will further demonstrate that Alzheimer’s disease may not be the same disease in men and women. By understanding the specifics of the disease in each sex, we will develop better therapies to treat everyone suffering from this disease.
MOSH Award – Tara DeSilva, PhD
My name is Tara DeSilva and I am a neuroscientist at the Cleveland Clinic. I would like to thank the Women’s Alzheimer’s Movement Movement and MOSH for supporting our research on sexual dimorphism in microbial metabolites from Alzheimer’s disease postmortem brains.
That’s a lot of science, so let me unravel that. Women are twice as likely to develop Alzheimer’s, but the cause of this disparity remains unclear. Many cases of Alzheimer’s are associated with multiple genetic and environmental risk factors, suggesting that genetic variants alone are not enough to explain why some brains develop Alzheimer’s and some do not.
For instance, we know that chronic inflammatory metabolic conditions—such as hypertension, diabetes mellitus, arteriosclerosis, obesity, and hypercholesterolemia—are significant risk factors for the disease and share a common feature: gut dysbiosis, or a gut that is out of balance. That’s important because the gut microbiome is composed of diverse microbes including bacteria, and it plays a crucial role in metabolizing food and producing metabolites—or byproducts—that can influence brain health. However, which of those microbial byproducts reach the brain and how they are altered in the brains of people with Alzheimer’s is still unknown.
Our findings to date reveal that there are sex-specific differences in microbial metabolites in Alzheimer’s brains, particularly those associated with cardiovascular disease and stroke. This MOSH grant will allow us to further investigate those sex differences in microbial-derived metabolites in post-mortem Alzheimer’s brains and blood, as well as in Alzheimer’s models before and after the development of brain pathology. The end goal is to identify early, blood-based biomarkers predictive of Alzheimer’s risk in women and support the development of nutritional or therapeutic interventions in hopes of preventing the disease from developing in the first place.