Scientists from the Baylor College of Medicine are revealing how the fungus Candida albicans enters the brain, triggers mechanisms that aid in its clearance, and generates toxic protein fragments known as amyloid beta (Ab)-like peptides — a key player in Alzheimer's disease development.

"Our lab has years of experience studying fungi, so we embarked on the study of the connection between C. albicans and Alzheimer's disease in animal models," says study corresponding author Dr. David Corry, the Fulbright Endowed Chair in Pathology and a professor of pathology and immunology and medicine at Baylor, in a university 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."

The study first sought to unravel how Candida albicans gains access to the brain. Researchers discovered that the fungus produces enzymes called secreted aspartic proteases (Saps), which break down the blood-brain barrier — a protective barrier that usually prevents harmful substances from entering the brain. This breach allows the fungus to infiltrate the brain and cause damage.

The next question posed by the researchers was how the brain effectively clears the fungus. Previous research has shown that C. albicans brain infections resolve entirely in healthy mice after 10 days. In this study, the team unveiled two mechanisms triggered by the fungus in microglia brain cells, which play a crucial role in the brain's immune response.

"The same Saps that the fungus uses to break the blood-brain barrier also break down the amyloid precursor protein into Ab-like peptides," says study first author Dr. Yifan Wu, postdoctoral scientist in pediatrics working in the Corry lab. "These peptides activate microglial brain cells via a cell surface receptor called Toll-like receptor 4, which keeps the fungi load low in the brain, but does not clear the infection."