Unraveling the Enigma: How Fungal Infections Resemble Alzheimer’s Disease in the Brain

A recent investigation by scholars at Baylor College of Medicine has delved into the potential connection between the fungus Candida albicans and the onset of Alzheimer’s disease. Employing animal models in their research, they unveiled a startling revelation: this fungus possesses the ability to breach the formidable blood-brain barrier through the use of enzymes and subsequently generate amyloid beta (Ab)-like peptides, the notorious toxic protein fragments implicated in the pathology of Alzheimer’s.

Intriguingly, the study emanating from Baylor College of Medicine shines a spotlight on the capacity of Candida albicans to produce these deleterious peptides linked to Alzheimer’s disease. This newfound insight beckons forth the imperative for further investigation into potential therapeutic avenues.

Prior studies have hinted at the involvement of fungi in chronic neurodegenerative conditions, including Alzheimer’s disease. However, our understanding of the precise role these ubiquitous microorganisms play in the development of such ailments remains limited.

Harnessing animal models as their experimental canvas, researchers hailing from Baylor College of Medicine and collaborating institutions deciphered the intricate mechanisms through which Candida albicans infiltrates the brain. It triggers two distinct mechanisms within brain cells that facilitate its clearance. Notably, it also engenders amyloid beta (Ab)-like peptides, which are pernicious protein fragments derived from the amyloid precursor protein and are believed to be pivotal in the genesis of Alzheimer’s disease. This groundbreaking study was published on October 10 in the esteemed journal Cell Reports.

The Nexus Between Fungus and Alzheimer’s Disease

Dr. David Corry, the corresponding author of the study and Fulbright Endowed Chair in Pathology and professor of pathology and immunology and medicine at Baylor, elucidated, “Our lab boasts a wealth of experience in the realm of fungi, prompting our investigation into the interplay between C. albicans and Alzheimer’s disease within animal models.” He further emphasized, “In 2019, we reported that C. albicans indeed infiltrates the brain and induces changes strikingly akin to those observed in Alzheimer’s disease. The present study extends this inquiry to decipher the molecular underpinnings.”

The initial query that guided their investigation was, how does C. albicans manage to breach the brain’s formidable defenses? The researchers uncovered that C. albicans secretes enzymes known as secreted aspartic proteases (Saps) to dismantle the impervious blood-brain barrier, thereby gaining access to the brain and inducing harm. Dr. Yifan Wu, the first author and a postdoctoral scientist in pediatrics working in Dr. Corry’s lab, elucidated, “These Saps, responsible for breaching the blood-brain barrier, also cleave the amyloid precursor protein into AB-like peptides.” Wu added, “These peptides, in turn, activate microglial brain cells via the cell surface receptor known as Toll-like receptor 4, thereby maintaining a low fungal load in the brain, although they do not completely eradicate the infection.”

Notably, Candida albicans also produces a protein called candidalysin, which binds to microglia through a different receptor known as CD11b. Dr. Wu emphasized, “The activation of microglia by candidalysin is instrumental in clearing Candida from the brain. If we disrupt this pathway, fungi persist in the brain.”

Novel Insights into Alzheimer’s Disease Development

Dr. Corry asserted, “This research potentially furnishes a significant puzzle piece in our quest to comprehend the genesis of Alzheimer’s disease.” The conventional theory posits that this ailment primarily ensues from the accumulation of toxic Ab-like peptides in the brain, leading to neurodegeneration. It is widely believed that these peptides are internally generated within the brain as a result of proteases breaking down the amyloid precursor proteins.

However, the current study challenges this prevailing notion by demonstrating that Ab-like peptides can also originate from a different source – Candida albicans. This ubiquitous fungus, previously detected in the brains of individuals afflicted with Alzheimer’s disease and other chronic neurodegenerative disorders, possesses its own array of proteases capable of generating the same Ab-like peptides that the brain can produce endogenously.

Dr. Corry concluded, “We postulate that the aggregates of brain Ab-peptides, hallmarking multiple neurodegenerative conditions associated with Candida, including Alzheimer’s disease and Parkinson’s disease, may arise both intrinsically within the brain and from the influence of C. albicans.” These compelling findings in animal models beckon for further investigations to assess the role of Candida albicans in the development of Alzheimer’s disease in humans, potentially paving the way for innovative therapeutic strategies.

Reference: “Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis” by Yifan Wu, Shuqi Du, Lynn H. Bimler, Kelsey E. Mauk, Léa Lortal, Nessim Kichik, James S. Griffiths, Radim Osicka, Lizhen Song, Katherine Polsky, Lydia Kasper, Peter Sebo, Jill Weatherhead, J. Morgan Knight, Farrah Kheradmand, Hui Zheng, Jonathan P. Richardson, Bernhard Hube, Julian R. Naglik, and David B. Corry, 10 October 2023, Cell Reports.
DOI: 10.1016/j.celrep.2023.113240

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More about Alzheimer’s-Fungus Link

• Baylor College of Medicine
• Cell Reports Journal
• Candida albicans
• Alzheimer’s Disease
• Blood-Brain Barrier
• Microglia
• Amyloid Precursor Protein
• Toll-like Receptor 4
• CD11b Receptor
• Neurodegenerative Disorders
• Parkinson’s Disease
• Innovative Therapeutic Strategies