Could Alzheimer’s be Linked to Fungal Infections?

In a study, researchers shed light on the role of Candida as a possible Alzheimer’s trigger

In the search for the causes of Alzheimer’s and other dementias, a common inhabitant of the human organism has become the focus of research: Candida albicans. According to a new study published in “Cell Reports”, it could also contribute to the formation of amyloid plaques.

The accumulation of incorrectly folded β-amyloid is not the only trigger for Alzheimer’s dementia. The so-called amyloid hypothesis is still highly controversial, but appears to play a cardinal role in the development process. The plaques initiate a series of further processes that ultimately lead to the death of nerve cells and thus cause the symptoms of dementia.

Earlier research showed that fungal fragments accumulate in brains affected by Alzheimer’s

In 2016, research results had already shown that protein fragments of various types of fungi, including Candida albicans, accumulate in the brains of Alzheimer’s patients. In contrast, hardly any fungal proteins were found in healthy test subjects. This may indicate that recurrent or persistent Candida infections could contribute to the development of Alzheimer’s dementia. However, it was previously unclear how Candida could influence Alzheimer’s dementia. An American research group has now identified a mechanism that links infection of the brain by Candida with the formation of amyloid plaques.

Candida albicans and other fungal species are part of the normal microflora of the human body and usually live in harmony with other microorganisms. However, they are opportunistic, which means that they can lead to infections if the immune system is weakened or if there are changes in the microflora.

Candida albicans can break through the blood-brain barrier

An American research team from Baylor College of Medicine, Houston, Texas, has now uncovered a mechanism in a further study that shows how an infection of the brain by Candida albicans is linked to the formation of amyloid plaques, as they occur in Alzheimer’s disease. The researchers discovered that Candida albicans releases enzymes that can cross the blood-brain barrier.

The enzymes produced by Candida albicans, known as Saps (secreted aspartic proteinases), initially enable the fungus to cross the blood-brain barrier. They do this by destroying components of the barrier, making it more permeable. After C. albicans has penetrated the brain, the effect of the saps enzymes continues. Among other things, they break down the amyloid precursor protein (APP) into β-amyloid, which plays a role in the development of Alzheimer’s dementia. These peptides stimulate the brain’s immune cells, the microglia, to reduce the fungal load, but without completely eliminating the infection. The study suggests that the amyloid beta aggregates found in Alzheimer’s may be produced by both the human brain and Candida albicans.

“This work potentially contributes to an important new piece of the puzzle regarding the development of Alzheimer’s disease,” said corresponding author Dr. David Corry of the Fulbright Endowed Chair in Pathology and professor of pathology, immunology and medicine at Baylor University in a press release.

New model for the development of β-amyloid plaques as a hypothesis for future research

One limitation of the study is that the results are based on investigations in cell cultures and mice, which is why the transferability to humans is still uncertain. Nevertheless, the researchers propose a new model for the development of β-amyloid plaques as a hypothesis for future research.

Until now, it was assumed that these amyloid proteins are produced exclusively in the body itself by the body’s own proteases degrading amyloid precursor proteins and thereby creating toxic β-amyloid proteins. However, the current research results suggest that the β-amyloid aggregates present in the brain, which are characteristic of neurodegenerative diseases such as Alzheimer’s, could be produced both by the brain itself and by C. albicans.