Alzheimer's: Fungal infection may trigger toxic proteins
- Researchers have uncovered how a common fungus enters the brain and generates toxic proteins implicated in Alzheimer’s disease.
- By studying animal models, the team found that the fungus Candida albicans uses enzymes to penetrate the blood-brain barrier and trigger brain cells to both clear the infection and produce amyloid beta peptides.
- The findings reveal a potential new mechanism behind Alzheimer’s development, which could open new avenues for novel treatment strategies.
Scientists at Baylor College of Medicine in Houston and collaborating institutions discovered how Candida albicans enters the brain and triggers two separate mechanisms that promote its clearance.
Previous research has linked fungi to chronic neurodegenerative conditions like Alzheimer’s disease, but there is limited understanding of how these common microbes could contribute to the development of such conditions.
In this new study, published in Cell Reports, the researchers investigated the connection between C. albicans and Alzheimer’s disease in animal models.
C. albicans is a yeast — a type of single-celled fungus — and is part of the natural microflora, which are the microorganisms that inhabit the body.
In normal amounts, C. albicans usually does not cause any problems. However, overgrowths can occur, leading to infections.
The fungus, which has been detected in the brains of individuals with Alzheimer’s disease, can produce amyloid proteins similar to those that build up in the brains of people with Alzheimer’s disease.
Amyloid may be generated from two sources
“We wanted to know through this work how the body fights off this very important fungus, Candida albicans, which infects all persons, to the best of our knowledge,” said senior author Dr. David B Corry.
“We showed earlier that Candida gets into the mouse brain from the blood, so here we wanted to know how the brain fights off the fungus,” Dr. Corry explained.
Dr. Corry then pointed out the key findings of this new research to Medical News Today.
He told us that, first, C. albicans secretes enzymes that break down the blood-brain barrier, allowing the fungus to enter the brain.
Microglia, the brain’s infection-fighting cells, detect C. albicans through interactions between candidalysin, a Candida protein, and CD11b, a microglial protein. This triggers the microglia to eliminate the fungus.
Microglia also detect C. albicans through a second pathway — Candida proteinases cleave amyloid precursor protein on neurons into fragments that signal through toll-like receptor 4 on microglia, activating fungal killing.
Importantly, these fragments are similar to those found in Alzheimer’s patients, suggesting that Candida proteinases may contribute to the cognitive decline in Alzheimer’s by generating these neurotoxic fragments.
How Candida breaks through the blood-brain barrier
Dr. Heather Sandison, a naturopath who specialises in dementia care, not involved in this research, said that the current study “further validates previous research suggesting candidiasis can be related to the development of Alzheimer’s disease by triggering the production of amyloid beta, which acts as a defense against candida and other microbes in the brain.”
“This paper describes the mechanism by which Candida directly degrades the blood-brain barrier that is meant to protect the brain from infections like candida,” she added. “Additional testing in this paper also shows that when the blood-brain barrier is compromised for other reasons, Candida is more likely to enter the brain.”
Dr. James Giordano, professor in the departments of neurology and biochemistry at Georgetown University Medical Center in Washington, also not involved in this research, commented that “this study, using a mouse model, coupled to in vitro experiments, shows that the fungus C. albicans gains access from the blood stream to the brain [presumably] by producing peptides that compromise the integrity of the blood-brain barrier.”
“Further, this study demonstrated that C. albicans produces other peptides that can activate amyloid pathways that are involved in neuroinflammatory and neurodegenerative conditions, including Alzheimer’s — and other forms of —dementia,” Dr. Giordano explained.
Potential implications for developing new treatment strategies
Dr. Corry highlighted that “our findings suggest, but do not [yet] prove, that infections related to Candida albicans can be detrimental to brain health.”
“Because of the link to Alzheimer’s disease as suggested by the fragments created by the fungus and the additional evidence presented by other groups suggesting that C. albicans is in fact present in the Alzheimer’s disease brain, our findings provide further evidence linking C. albicans to Alzheimer’s disease.”
– Dr. David B. Corry
“Our work has emphasized how the brain rids itself of Candida, but they suggest specific ways of improving these pathways to more effectively counter the fungus,” he further explained.
Dr. Sandison further noted that “this is a mouse model, and although the research in mice models does not always translate to human models, this research offers a reminder to avoid candidiasis generally.”
“Strategies for avoiding Candida growth include a low-sugar diet, avoid overuse of antibiotics or immunosuppressive medications like steroids, use probiotics or fermented foods following a course of antibiotics, consider increasing your consumption of foods and herbs with natural antifungal properties like coconut oil, garlic, and oregano,” Dr. Sandison highlighted.
Although several studies have shown links between microbes and Alzheimer’s disease, there are many modifiable risk factors that are associated with Alzheimer’s, explained Dr. Sandison.
These include sleep deprivation, type 2 diabetes, high blood pressure, sedentary lifestyle, excess weight, hearing loss, and social isolation.
“I recommend my patients focus on the modifiable risk factors they can control to reduce their risk of dementia as much as possible as they age,” she told us.
Dr. Giordano concluded that “this research further clarifies the mechanisms by which microglia — immunological cells of the brain — initiate and sustain responses to suppress the pathologic effects of the fungus C. albicans.”
“These findings, although demonstrated in a mouse model, may be important to advancing human research that could lead to improved therapeutics against cerebral fungal infections, which can occur in immunocompromised, and/or chronically ill, hospitalized patients.”
– Dr. James Giordano
Source: Read Full Article
