"The groundwork of all happiness is health." - Leigh Hunt

Fungal infection within the brain causes the changes seen in Alzheimer's disease.

Previous research has implicated fungi in chronic neurodegenerative conditions corresponding to Alzheimer's disease, but there is restricted understanding of how these common microbes could also be involved in the event of those conditions.

Working with animal models, Baylor College of Medicine researchers and collaborating institutions discovered how the fungus enters the brain, activating two distinct mechanisms in brain cells that promote its clearance. , and produces amyloid beta (Ab), essential for understanding the event of Alzheimer's disease. Like peptides, toxic protein fragments from amyloid precursor proteins are considered central to the event of Alzheimer's disease. The study appears within the journal.

“Our lab has years of experience studying fungi, so we began studying the link between Alzheimer's and Alzheimer's disease in animal models,” said corresponding writer Dr. David Corey, Fulbright Endowed Chair in Pathology and Pathology and Professor of Immunology and Medicine said. Baylor. He can be a member of Baylor's Dan L Duncan Comprehensive Cancer Center. “In 2019, we reported that it enters the brain where it produces changes that are very similar to those seen in Alzheimer's disease. The current study extends this work to understand the molecular mechanisms involved.” “

“Our first question was how does it enter the brain? We found that enzymes called secreted aspartic proteases (Saps) are produced that break down the blood-brain barrier, giving the fungus access to the brain where it can cause damage. delivers,” said first writer Dr. Yifan Wu, a postdoctoral scientist in pediatrics working within the Corey lab.

Next, the researchers asked, how is the fungus effectively cleared from the brain? Corey and his colleagues previously showed that brain infection completely resolved after 10 days in healthy mice. In this study, they reported that this happened due to two mechanisms created by fungi in brain cells called microglia.

“The same saps that the fungus uses to breach the blood-brain barrier also break down amyloid precursor proteins into AB-like peptides,” Wu said. “These peptides stimulate microglial brain cells through a cell surface receptor called toll-like receptor 4, which keeps the fungal load in the brain low, but does not clear the infection.”

Also produces a protein called candidalysin that also binds to microglia through a special receptor, CD11b. “Candidalysin-mediated activation of microglia is essential for clearance in the brain,” Wu said. “If we take away this pathway, the fungus in the brain will not be cleared effectively.”

“This work potentially contributes an important new piece of the puzzle regarding the development of Alzheimer's disease,” Corey said. “The current explanation for this condition is that it is mostly the result of the accumulation of toxic Ab-like peptides in the brain that lead to neurodegeneration. The prevailing thought is that these peptides are produced endogenously, by our own brain protease amyloid. Precursor proteins that produce toxic Ab peptides.”

Here, the researchers show that Ab-like peptides can be produced from a special source. This common fungus, which has been present in the brains of individuals with Alzheimer's disease and other chronic neurodegenerative disorders, has its own set of proteases that may produce the identical Ab-like peptides that could be produced contained in the brain. Is.

“We propose that the brain Ab-peptide aggregates that characterize a number of neurodegenerative conditions, including Alzheimer's disease, Parkinson's disease and others, may be produced both endogenously and by the brain,” Cory said. ” “These findings in animal models support further studies to judge the role in the event of Alzheimer's disease in people, which could potentially result in revolutionary treatment strategies.”