Irvine, Calif., August 22, 2024 — In a significant breakthrough, researchers at the UC Irvine Charlie Dunlop School of Biological Sciences have discovered a promising new approach to treating Alzheimer’s disease, potentially slowing or even halting its progression. This research, led by Distinguished Professor Andrea Tenner and Professor Ali Mortazavi, focuses on mitigating the damaging inflammation in the brain, a key factor contributing to Alzheimer’s disease.
Alzheimer’s, the most common cause of dementia, affects millions of people globally, with no effective treatment currently available to stop its progression. One of the major challenges in combating Alzheimer’s is the harmful inflammation triggered by amyloid plaques and the death of neurons, which leads to the decline in memory and cognitive functions.
The research team identified a specific receptor in the brain called C5aR1 that, when activated, exacerbates this damaging inflammation. By blocking this receptor using an inhibitor, the researchers found they could prevent the harmful inflammatory response.
Professor Andrea Tenner elaborated on the significance of these findings: “Oral administration of an inhibitor of a membrane receptor results in protection from progressive synapse loss and cognitive deficits in mouse models of Alzheimer’s disease. The receptor, called C5aR1, binds a fragment, C5a, that is generated in response to the presence of amyloid plaques and dead and dying neurons characteristic of Alzheimer’s disease. Interaction of C5a with C5aR1 triggers inflammation that is known to be damaging to neurons, and thus over time, contributes to loss of memory and other mental processes.”
The study, with postdoctoral fellow, Nicole Schartz as first author of the manuscript, also revealed that while the C5aR1 inhibitor effectively blocked the detrimental inflammation, it allowed other brain cells to continue their beneficial, neuroprotective activities. “Distinct microglia and astrocytes subtypes were identified in an Alzheimer’s disease mouse model only when C5a-C5aR1 signaling was permitted,” Professor Tenner explained. “Other subtypes of microglia and astrocytes were identified that responded to the ‘injury’ of amyloid deposits that functioned in a beneficial neuroprotective fashion. Those ‘good’ cells retained protective responses in the presence of the C5aR1 inhibitor.” This approach not only protected against progressive synapse loss but also preserved cognitive function in mouse models of Alzheimer’s disease.
The implications of this research are profound. If these findings translate to humans, they could lead to a new therapeutic strategy for Alzheimer’s and potentially other neurodegenerative diseases. Professor Tenner highlighted the importance of these results for future clinical applications: “Importantly, all these beneficial effects were seen with adult administration of the drug after the onset of plaque deposition in mouse models, which mimics the time at which patients begin to exhibit signs of Alzheimer’s disease. As a result, the findings are promising as a treatment to prevent or slow the progression of Alzheimer’s disease and provide rationale for clinical trials.”
There is growing hope that this innovative approach could offer a new avenue for treating not only Alzheimer’s disease but other related neurodegenerative disorders. Professor Tenner concluded, “The potential translational value of these studies is that specifically targeting C5aR1 inhibits excessive/detrimental responses to injury while leaving the beneficial/neuroprotective responses to injury intact.”
This discovery, recently published in Nature Communications, represents a significant step forward in the fight against Alzheimer’s disease, offering renewed hope for patients and their families. Further research and support from the scientific community and policymakers will be crucial to advancing this promising treatment towards clinical application.
This study was funded by grants from the National Institutes of Health, the Alzheimer’s Association, the Larry L. Hillblom Foundation, and the Edythe M. Laudati Memorial Fund. Additional support was provided by the University of California, Irvine.
About the University of California, Irvine Charlie Dunlop School of Biological Sciences:
Recognized for its pioneering research and academic excellence, the Charlie Dunlop School of Biological Sciences plays a crucial role in the university’s status among the nation’s top 10 public universities, as ranked by U.S. News & World Report. It offers a broad spectrum of degree programs in the biological sciences, fostering innovation and preparing students for leadership in research, education, medicine and industry. Nestled in a globally acclaimed and economically vibrant community, the school contributes to the university’s impact as Orange County’s largest employer and a significant economic contributor. Through its commitment to exploring life’s complexities, the Dunlop School embodies the UCI legacy of innovation and societal impact. For more on the Charlie Dunlop School of Biological Sciences, visit https://www.bio.uci.edu/.