June 20, 2024
New Study Reveals Link Between Fungal Infections and Alzheimer's Disease

New Study Reveals Link Between Fungal Infections and Alzheimer’s Disease

Researchers from Baylor College of Medicine have discovered a connection between the fungus Candida albicans and the development of Alzheimer’s disease. The study suggests that this common fungus can produce toxic peptides that are associated with Alzheimer’s disease, indicating a potential role in its progression.

While previous research has suggested a link between fungi and chronic neurodegenerative conditions like Alzheimer’s disease, little is known about how these microbes may contribute to the development of these conditions.

Using animal models, the researchers found that Candida albicans enters the brain and activates two separate mechanisms in brain cells that help eliminate the fungus. Importantly, the fungus also generates amyloid beta (Ab)-like peptides, which are toxic protein fragments that are considered to be at the core of Alzheimer’s disease development. The findings of the study were published in the journal Cell Reports on October 10.

Dr. David Corry, the corresponding author of the study and a professor of pathology and immunology at Baylor College of Medicine, explained that their laboratory has been studying fungi for years, which led them to investigate the connection between Candida albicans and Alzheimer’s disease in animal models. In a previous study in 2019, they found that Candida albicans enters the brain and causes changes similar to those seen in Alzheimer’s disease. The current study expands on that work by uncovering the molecular mechanisms involved.

The initial question the researchers sought to answer was how Candida albicans enters the brain. They discovered that the fungus produces enzymes known as secreted aspartic proteases (Saps) that break down the blood-brain barrier, allowing the fungus to penetrate the brain and cause damage.

The researchers then investigated how the brain effectively clears the fungus. They found that microglia, a type of brain cell, are activated by the Candida albicans-produced AB-like peptides through a cell surface receptor called Toll-like receptor 4. This activation helps keep the fungal load low in the brain but does not completely clear the infection. Additionally, Candida albicans produces a protein called candidalysin that binds to microglia through a different receptor known as CD11b. Activation of microglia through candidalysin is essential for effectively clearing the fungus from the brain.

These findings provide new insights into the development of Alzheimer’s disease. It is currently believed that the accumulation of toxic AB-like peptides in the brain leads to neurodegeneration in Alzheimer’s disease. However, the researchers demonstrate that these peptides can also be generated by Candida albicans. This fungus, which has been found in the brains of individuals with Alzheimer’s disease and other neurodegenerative disorders, possesses its own set of proteases that can produce the same AB-like peptides as the brain itself.

The researchers propose that the AB-peptide aggregates observed in various Candida-associated neurodegenerative conditions, including Alzheimer’s disease and Parkinson’s disease, may be generated both intrinsically by the brain and by Candida albicans. These findings in animal models emphasize the need for further studies to explore the role of Candida albicans in the development of Alzheimer’s disease in humans, which could potentially lead to innovative therapeutic strategies.

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