A new study in mice reveals that Candida albicans — a fungus largely perceived as harmless — can cause memory problems and brain abnormalities that resemble those characteristic of Alzheimer's disease.
Candida albicansis a species of fungus that grows naturally in the human gut, mouth, and vagina.
Although the yeast is mostly harmless, it can develop into issues ranging from thrush to more serious infections that reach the blood and other organs.
C. albicans is the most common cause of fungal infections in humans, as well as the most extensively studied fungal pathogen that affects people.
The new research shows that the fungus can enter the brain, trigger an inflammatory response, and impair memory in mice.
Importantly, the infection leads to the formation of abnormal structures in the brain, and these share similarities with amyloid plaques — a hallmark of Alzheimer's disease.
Dr. David B. Corry, a professor of medicine-immunology, allergy, and rheumatology at the Baylor College of Medicine in Houston, TX, is the corresponding and final author of the new study.
Why study C. albicans and the brain?
Dr. Corry explains the motivation for the research, pointing to the link between fungi, respiratory infections, and dementia.
He says, "An increasing number of clinical observations [...] indicates that fungi are becoming a more common cause of upper airway allergic diseases such as asthma, as well as other conditions such as sepsis, a potentially life-threatening disease caused by the body's response to an infection."
"These observations," continues Dr. Corry, "led us to investigate the possibility that fungus might produce a brain infection and, if so, the consequences of having that kind of infection."
The corresponding researcher also highlights the fact that sepsis and allergic respiratory infections caused by fungi have correlated with a higher risk of dementia in previous studies.
How C. albicans affects the brain, memory
Dr. Corry and colleagues tested several doses of C. albicans in a mouse model of the infection. They were trying to find a dose that would be high enough to affect the brain, but not high enough to cause debilitating disease.
Finally, the scientists decided to inject a dose of 25,000 yeasts in the rodents' bloodstream. Dr. Corry and the team were surprised to discover that the fungus penetrated the blood-brain barrier.
The blood-brain barrier is a mechanism that protects the brain from pathogens that may exist in the blood. The barrier separates the brain's capillaries, or blood vessels, from the brain's cells and tissue.
C. albicans crossed this barrier and affected the brain's immune cells. "We thought that yeast would not enter the brain, but it [did]," comments Dr. Corry.
"In the brain, the yeast triggered the activity of microglia, a resident type of immune cell," he explains, adding, "[t]he cells became very active, 'eating and digesting' the yeast. They also produced a number of molecules that mediated an inflammatory response, leading to the capture of the yeasts inside a granule-type structure inside the brain."
The researchers called this structure "fungus-induced glial granuloma, or FIGG." The scientists also noticed that, as FIGGs formed, amyloid precursor proteins and molecules of a protein called amyloid beta developed around the yeast cells.
Similarities with Alzheimer's disease
Amyloid beta and amyloid precursor proteins form the toxic brain plaques that characterize Alzheimer's disease.
Also, the scientists tested the mice's memory, comparing the infected rodents with rodents that did not have the yeast infection.
Mice that had the infection showed reduced spatial memory. However, when the infection cleared, the mice's spatial memory went back to normal.
"These findings suggest that the role fungi play in human illness potentially goes well beyond allergic airway disease or sepsis," Corry says.
"The results prompted us to consider the possibility that in some cases, fungi also could be involved in the development of chronic neurodegenerative disorders, such as Alzheimer's, Parkinson's, and multiple sclerosis. We are currently exploring this possibility."
Dr. David B. Corry
"[I]f we better understand how our immune system deals with this kind of constant threat and what are the weaknesses in our immunological armor that occur with aging [and] allow fungal disease to take root, then we would likely increase the possibility of finding ways to fight back, " adds Dr. Corry.