A disturbing new study found that the common fungus Candida albicans (C. albicans) can enter the brain and trigger a cascade of events that may lead to Alzheimer’s disease. Scientists from Baylor College of Medicine reveal that as the brain endeavors to clear the fungus, toxic protein fragments known as amyloid beta (Ab)-like peptides are generated. These fragments are key players in the development of Alzheimer’s disease.

According to Study Finds, researchers previously discovered that C. albicans gains access to the brain by producing enzymes called secreted aspartic proteases (SAPs) that break down the blood-brain barrier, allowing the fungus to enter. The latest study, published in Cell Reports reveals how the brain tries to clears the fungus, but in doing so, can contribute to the development of Alzheimer's disease.

“Our lab has years of experience studying fungus, so we embarked on the study of the connection between C. albicans and Alzheimer’s disease in animal models,” said study author Dr. David B. Corry, a professor of pathology, immunology and medicine at Baylor in a news release. “In 2019 we reported that C. albicans does get into the brain where it produces changes that are very similar to what is seen in Alzheimer’s disease. The current study extends that work to understand the molecular mechanisms.”

Researchers say that the same SAPs that break down the blood-brain barrier also break down the amyloid precursor protein into Ab-like peptides. These peptides activate microglial brain cells through a cell surface receptor called toll-like receptor 4, which keeps the fungal load low in the brain, but doesn’t clear the infection.

C. albicans also produces a protein called candidalysin that binds to the microglia through a different receptor called CD11b that is critical in removing Candida from the brain. If that pathway is disturbed, fungi are no longer effectively cleared in the brain.

Corry says his research explores a new piece of the puzzle in the development of Alzheimer’s disease by demonstrating that C. albicans can generate Ab-like peptides in the brain. The common fungus has been found in the brains of people with Alzheimer’s disease and other chronic neurodegenerative disorders. The prevalent theory is that Alzheimer’s disease is primarily driven by the accumulation of toxic Ab-like peptides in the brain that leads to neurodegeneration and that these peptides are produced internally by the brain. However, the new research sheds light on another potential mechanism.

“We propose that the brain Ab-peptide aggregates that characterize multiple Candida-associated neurodegenerative conditions including Alzheimer’s disease, Parkinsons’s disease and others, may be generated both intrinsically by the brain and by C. albicans,” said Corry, according to the news release.