With research reporting that Candida albicans has been found in the brains of some patients with Alzheimer’s disease and other neurodegenerative disorders despite any obvious signs of acute illness, researchers have taken more interest in understanding the mechanisms behind this correlation. Alzheimer’s disease has been on the rise for decades, and so have its correlations with various infectious agent. Follow up studies on those who experienced such fungal infections early in life shows increases in dementia years later, but more recent research indicates that even without an obvious infection, candida may invade the brain and contribute to future dementia. This study looked at potential mechanisms by which C. albicans, a common fungus in our bodies, might lead to such neurologic changes.
Normally, the blood brain barrier offers strong protection for the brain against a huge variety of pathogens such as bacteria, viruses, and fungi. On the brain side of the blood-brain barrier, damage could cause permanent dysfunction and our immune systems inside brain tissue are more limited than in the rest of the body. Inside the brain, we are mainly dependent on immune cells called microglia to deal with infections. These microglia act to attack and clean up both invaders and any potential inflammatory chemicals floating around. Inadequate microglia response can allow harmful pathogens or chemicals to continue their adverse effects, while overactive responses can cause autoimmune conditions like multiple sclerosis. As is often the case, balanced function in the middle of the road is critical.
While we had relatively detailed understanding of how our peripheral immune system responds to fungal infections in the body, we did not fully understand how microglia in the brain controlled fungal infections there. We also did not fully understand how C. albicans entered the brain in the first place. This study shed light in these areas and explains the potential for C. albicans contribution to Alzheimer’s disease.
With the help of secreted aspartic proteinases (Saps), candida breaks open the tight junctions between capillary endolethial cells serving as the blood brain barrier. Once across the barrier, these same Saps enzymes decrease amyloid precursor protein into amyloid beta like peptides. These peptides bind an immune receptor called Toll-like receptor 4 which activates microglial cells. These amyloid beta peptides appear to play a role in the pathogenesis of Alzheimer’s disease so that is the first connection.
In most cases, the candida secrete a protein called candidalysin, inducing the microglia to attack the candida. When this pathway is intact, the brain clears out the candida relatively rapidly, and the acute infection ends. If this pathway does not work, at least in mice models, the candida infection continues in the long term. The authors of this study noted that C. albicans appears to be able to persist lifelong in some organs despite all the immune mechanisms capable of eradicating it. They also noted that no science has yet proven that the amyloid beta proteins produced in the process of attacking C. albicans is the exact same of the amyloid beta that accumulates in neurodegenerative disorders like Alzheimer’s disease, there are strong reasons to suspect connections.
With much more research to be done, we cannot definitively connect C. albicans infection anywhere in the body with Alzheimer’s, but we cannot ignore the possibility as we care for patients with yeast overgrowth. Conventional medicine focuses on the obvious acute infections of candida and other fungi, but this study suggests that low grade and prolonged presence of candida may have as yet underappreciate contributions to neurodegenerative disease. In helping our patients restore healthier more abundant lives, we have to keep all of this in perspective treating each patient with all the tools available. This is especially true for neurodegenerative diseases like Alzheimer’s where our understanding is incomplete and the stakes high.
Original Article:
Yifan Wu et al. Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis. Cell Reports, 2023 DOI: 10.1016/j.celrep.2023.113240
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.
