![David B. Corry, M.D. Professor of Pathology & Immunology and Medicine Vice Chair for Immunology Department of Pathology & Immunology Biology of Inflammation Center Dan L. Duncan Comprehensive Cancer Center Clarence and Irene H. Fulbright Chair in Pathology Baylor College of Medicine Michael E. Debakey VA Medical Center](https://medicalresearch.com/wp-content/uploads/2023/10/David-B-Corry.jpeg)
22 Oct Baylor College of Medicine Scientists Find Potential Link Between Common Fungus and Alzheimer’s
MedicalResearch.com Interview with:
![David B. Corry, M.D.Professor of Pathology & Immunology and Medicine Vice Chair for Immunology Department of Pathology & Immunology Biology of Inflammation Center Dan L. Duncan Comprehensive Cancer Center Clarence and Irene H. Fulbright Chair in Pathology Baylor College of Medicine Michael E. Debakey VA Medical Center](https://medicalresearch.com/wp-content/uploads/2023/10/David-B-Corry.jpeg)
Dr. Corry
David B. Corry, M.D.
Professor of Pathology & Immunology and Medicine
Vice Chair for Immunology
Department of Pathology & Immunology
Biology of Inflammation Center
Dan L. Duncan Comprehensive Cancer Center
Clarence and Irene H. Fulbright Chair in Pathology
Baylor College of Medicine
Michael E. Debakey VA Medical Center
MedicalResearch.com: What is the background for this study? Can candida species cross the blood brain barrier?
Response: We showed earlier (2019) that the common fungus Candida albicans can enter the brain from the blood. That earlier study was in turn inspired by the finding of another research group that had found Candida in the brains of persons suffering from Alzheimer’s Disease and related dementing illnesses.
MedicalResearch.com: What are the key findings?
Response: We wanted to know through this work how the body fights off this very important fungus, Candida albicans, which infects all persons, to the best of our knowledge. We showed earlier that Candida gets into the mouse brain from the blood, so here we wanted to know how the brain fights off the fungus. We discovered three major things:
a) how Candida gets through the protective barrier surrounding the brain (called the blood brain barrier) that normally prevents infections from getting through. We found that it is enzymes (proteinases) made by the candida that essentially dissolve away the blood brain barrier to enter the brain proper.
b) one way the brain infection-fighting cells (called microglia) detect Candida is through one of the main proteins secreted by Candida, called candidalysin. We found another protein on microglia that detects the candidalysin (called CD11b), essentially sending a signal to the microglia to go on high alert and begin killing off the fungus.
c) We found a second pathway through which microglia detect and begin killing the Candida. This pathway again involves the proteinases made by Candida (called secreted aspartic proteinases or Saps), but here the proteinases digest, or cleave, a protein found on brain neurons (called amyloid precursor protein; neurons allow us to think and learn) into small fragments. These fragements then signal through another protein found on microglia (called Toll like receptor 4; TLR4) to activate fungal killing.
The additional importance of this finding is that the fragments created by the Candida Saps are essentially the same as those found in the brains of Alzheimer’s Disease patients and it is these fragments that are believed to cause the brain dysfunction leading to memory loss and cognitive decline that is what Alzheimer’s Disease is all about. Prior to this work, the fragments were only thought to be created through human enzymes (proteinases); ours is the first report to show that there is a microbial (fungal) pathway that leads to the creation of the fragments.
MedicalResearch.com:What are the potential implications of your research for patients and the public?
Response: Our findings suggest, but do not (yet) prove, that infections related to Candida albicans can be detrimental to brain health. Because of the link to Alzheimer’s disease as suggested by the fragments created by the fungus and the additional evidence presented by other groups suggesting that Candida albicans is in fact present in the Alzheimer’s Disease brain, our findings provide further evidence linking Candida albicans to Alzheimer’s Disease. Our work has emphasized how the brain rids itself of Candida, but they suggest specific ways of improving these pathways to more effectively counter the fungus.
In very brief summary, our work has shown how the fungus Candida albicans enters the brain from the blood and two new ways by which brain cells fight off this fungus. Our findings further suggest new ways to improve defenses against Candida, a very common fungus that likely infects all persons and could be an underlying cause of diverse, currently unexplained, diseases the brain and other organs.
I have no disclosures.
Citation:
Wu et al., 2023, Cell Reports 42, 113240 October 31, 2023 ª 2023 The Author(s). https://doi.org/10.1016/j.celrep.2023.113240
https://www.cell.com/cell-reports/pdf/S2211-1247(23)01252-4.pdf
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Last Updated on October 22, 2023 by Marie Benz