Fungal Infection In Neural Tissue Of Patients With Amyotrophic Lateral Sclerosis

[Makrosky]

Recently published study

@haidut you might like this

Link to the study

Highlights
•Tissue sections from different regions of the CNS of ALS patients contain fungi.
•These fungi are detected by immunohistochemistry with several antifungal antibodies.
•Some fungi are intracellular indicating that this is not a post-mortem colonization.
•CNS tissue from control subjects does not exhibit this burden of fungal infection.
•The species present in CNS tissue have been identified by next generation sequencing.
Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease and the main cause of motor neuron pathology. The etiology of the disease remains unknown, and no effective therapy exists to halt the disease or improve the quality of life. Here, we provide compelling evidence for the existence of fungal infection in ALS. Immunohistochemistry analysis using a battery of antifungal antibodies revealed fungal structures such as yeast and hyphae in the motor cortex, the medulla and the spinal cord, in eleven patients with ALS. Some fungal structures were localized intracellularly and even intranuclearly, indicating that this infection is not the result of post-mortem colonization. By contrast, this burden of fungal infection cannot be observed in several CNS areas of control subjects. PCR analysis and next generation sequencing of DNA extracted from frozen neural tissue identified a variety of fungal genera including Candida, Malassezia, Fusarium, Botrytis, Trichoderma and Cryptococcus. Overall, our present observations provide strong evidence for mixed fungal infections in ALS patients. The exact mixed infection varies from patient to patient consistent with the different evolution and severity of symptoms in each ALS patient. These novel findings provide a logical explanation for the neuropathological observations of this disease, such as neuroinflammation and elevated chitinase levels, and could help to implement appropriate therapies.

 

[aguilaroja]

Recently published study

@haidut you might like this

Link to the study ....Overall, our present observations provide strong evidence for mixed fungal infections in ALS patients. The exact mixed infection varies from patient to patient consistent with the different evolution and severity of symptoms in each ALS patient....

One question is whether fungal infection is a marker for depleted metabolism, or whether it is a main factor in inflammation that depletes metabolism.

From the same lab group:
Evidence for fungal infection in cerebrospinal fluid and brain tissue from patients with amyotrophic lateral sclerosis. - PubMed - NCBI
“…examination of brain sections from the frontal cortex of ALS patients revealed the existence of immunopositive fungal antigens comprising punctate bodies in the cytoplasm of some neurons. Fungal DNA was also detected in brain tissue using PCR analysis, uncovering the presence of several fungal species. Finally, proteomic analyses of brain tissue demonstrated the occurrence of several fungal peptides. Collectively, our observations provide compelling evidence of fungal infection in the ALS patients analyzed, suggesting that this infection may play a part in the etiology of the disease or may constitute a risk factor for these patients.”

Identification of Fungal Species in Brain Tissue from Alzheimer's Disease by Next-Generation Sequencing. - PubMed - NCBI
“whereas a great variety of species were identified using the Illumina platform, Botrytis cinerea and Cryptococcus curvatus were common to all four CNS regions analyzed. Further analysis of entorhinal/cortex hippocampus samples from an additional eight AD [Alzheimer's Disease] patients revealed a variety of fungal species, although some were more prominent than others. Five genera were common to all nine patients: Alternaria, Botrytis, Candida, Cladosporium, and Malassezia. These observations could be used to guide targeted antifungal therapy for AD patients.”

Corpora Amylacea of Brain Tissue from Neurodegenerative Diseases Are Stained with Specific Antifungal Antibodies. - PubMed - NCBI
“The origin and potential function of corpora amylacea (CA) remains largely unknown. Low numbers of CA are detected in the aging brain of normal individuals but they are abundant in the central nervous system of patients with neurodegenerative diseases.”
“CNS samples from patients diagnosed with amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) also contained CA that were immunoreactive with a range of antifungal antibodies. However, CA were less abundant in ALS or PD patients as compared to CNS samples from AD[Alzheimer's Disease].”