Cleveland Clinic researchers have identified sex-specific differences in brain immunometabolism—how the immune system interacts with cellular energy processes—that may contribute to women’s higher risk and faster progression of Alzheimer’s disease. Their findings, published in Alzheimer’s and Dementia, could guide the development of tailored treatments and prevention strategies for the disease, the sixth-leading cause of death in the U.S.
The study, a collaboration between Cleveland Clinic’s Lerner Research Institute and Lou Ruvo Center for Brain Health, analyzed brain tissue and genetic data from 469 Alzheimer’s patients. Researchers discovered that immune cells in the brain, particularly microglia, showed greater changes in women than in men, alongside sex-specific differences in immune function, cellular metabolism, and brain cell communication.
“Sex influences both immune systems and metabolic processes,” said Dr. Justin Lathia, co-author and vice chair of Cardiovascular and Metabolic Sciences. “Our study reveals how these factors interact to contribute to Alzheimer’s.”
“These findings are crucial for designing sex-specific medications and clinical trials,” added Dr. Feixiong Cheng, lead author and genomic medicine researcher. He and his team are investigating immune mechanisms and gut-brain interactions in Alzheimer’s, supported by $6.3 million and $4 million in NIH funding for two major projects.
Jessica Caldwell, Ph.D., director of the Women’s Alzheimer’s Movement Prevention Center at Cleveland Clinic, emphasized the importance of sex-based research. “Alzheimer’s is fundamentally a women’s health issue. Personalized care requires understanding how biological sex affects disease processes.”
This work aligns with Cleveland Clinic’s broader efforts, supported by NIH and Women’s Alzheimer’s Movement funding, to uncover the role of sex in neurodegenerative diseases and advance precision medicine.