Cleveland Clinic

Nov 24, 2023

Differences in brain immunometabolism may contribute to women’s increased risk for Alzheimer’s disease and its severity. News Thank you. Listen to this article using the player above. ✖ Want to listen to this article for FREE? Complete the form below to unlock access to ALL audio articles. ✖ Technology Networks Ltd. needs the contact information you provide to us to contact you about our products and services. You may unsubscribe from these communications at any time. For information on how to unsubscribe, as well as our privacy practices and commitment to protecting your privacy, check out our Privacy Policy Read time: 2 minutes Cleveland Clinic researchers analyzed genes and brain tissue of patients with Alzheimer’s and found that differences in brain immunometabolism – the interactions between the immune system and the ways cells create energy – may contribute to women’s increased risk for the disease and its severity. The findings, published in  Alzheimer’s and Dementia , offer important insight into developing sex-specific treatment and prevention options for Alzheimer’s disease, the sixth-leading cause of death in the United States. “Our immune systems depend on communication between different cell types in our bodies, which are fueled by energy created from unique metabolic processes,” said Justin Lathia, Ph.D., vice chair of the Department of Cardiovascular and Metabolic Sciences and co-author on the paper. “As sex influences both the immune system and metabolic process, our study aimed to identify how all of these individual factors influence one another to contribute to Alzheimer’s disease.” Want more breaking news? A collaboration between researchers in the Lerner Research Institute and physicians at the Lou Ruvo Center for Brain Health in Ohio and Nevada, the team analyzed brain samples and publicly available sequencing data obtained from 469 Alzheimer’s patients. They looked for changes in gene expression between males and females in immune function, cellular metabolism and communication between brain cells. They found sex-specific differences in all three areas with the notable difference in microglia – immune cells in the brain. Changes in microglia were greater in brains of female patients compared to males. “Women are more likely to develop Alzheimer’s disease, and experience faster cognitive decline compared to their male counterparts. These sex differences should be accounted for when designing medications and conducting clinical trials,” said Feixiong Cheng, Ph.D., Associate Staff, Genomic Medicine Institute and lead author of the paper. “These findings build on our knowledge of each part of the systems that play into Alzheimer’s and are critical to determining appropriate treatments.” This study was funded in part by a grant from the National Institutes of Health (R01AG084250) that supports the use of systems biology and multi-omics approaches to untangle the complex interactions between our immune systems, inflammation, and sex-based differences in Alzheimer’s disease. It is part of an ongoing effort between  Cleveland Clinic and the Women’s Alzheimer’s Movement  (WAM) to further understand the link between sex and all neurodegenerative conditions. “At its core, Alzheimer’s disease is a woman’s health issue. To address it, we must understand how biological sex contributes to the underpinnings of this disease,” said Jessica Caldwell, Ph.D., director of the WAM Prevention Center at Cleveland Clinic and another co-author on the paper. “These findings confirm that we need to look at sex differences in the way the body and brain systems communicate to be able to truly offer women personalized care and we look forward to continuing this research.” Reference: Hou Y, Caldwell JZK, Lathia JD, et al. Microglial immunometabolism endophenotypes contribute to sex difference in Alzheimer’s disease. Alzheimer’s & Dementia. 2023. doi:  10.1002/alz.13546 This article has been republished from the following materials . Note: material may have been edited for length and content. For further information, please contact the cited source. Advertisement