Cedars-Sinai study finds new way to combat Alzheimer’s in preclinical models

In a preclinical study, Cedars-Sinai investigators found that boosting angiotensin converting enzyme (ACE) in key immune cells called microglia in the brain helped protect the brains of specially bred laboratory mice against Alzheimer's disease. Their findings, published in Nature Aging, could lead to cellular therapies to help treat the disease in humans.

We found that by using gene editing to boost ACE in immune cells called microglia, which we believe become exhausted in the brains of patients with Alzheimer's disease, we supercharged those cells and seemed to restore them to full function. This allowed the microglia to clear the brain of the amyloid plaques associated with symptoms of Alzheimer's disease and to reverse neurodegeneration and cognitive decline."

Warren Tourtellotte, MD, PhD, professor of Pathology and Laboratory Medicine, Neurology, Neurosurgery, and Biomedical Sciences at Cedars-Sinai, and senior author of the study

To perform their experiments, investigators used genetic engineering to develop laboratory mice that accumulated amyloid plaques in their brains and overexpressed ACE in their microglia.

"The overexpression of ACE had a profound effect on the Alzheimer's-related brain changes in these mice," Tourtellotte said. "Their brains had fewer amyloid plaques and damage to neurons, and the connections between them appeared to be rescued. In addition, when ACE was expressed in microglia in these mice their performance in learning and memory tests was markedly improved."

The next step in this line of research is to show that this same biology exists in human microglia, Tourtellotte said. While more studies are needed, these findings might eventually lead to creation of a cell-based therapy that would work either independently or along with other Alzheimer's disease treatments.

"Scientific discovery is the key to developing treatments that will help us overcome Alzheimer's disease, which affects more than 7 million people in the U.S. and those who love them," said Nancy L. Sicotte, MD, chair of the Department of Neurology at Cedars-Sinai. "These findings, from the first pilot project to receive funding from the Jona Goldrich Center for Alzheimer's and Memory Disorders at Cedars-Sinai, point to a promising new direction for future work and possible new treatments."