https://drive.google.com/drive/u/1/folders/1zX2ieWLaUXsQOElqJn5aIqh06OJrCB7j

Comment; Fungal & polymicrobial fungal infections in the motor cortex, medulla & spinal cord in ALS patients not present in controls. I’ve heard reports of various oragnisms DNA being found in the parenchyma and CerebroSpinal Fluid of “normal” patients. I think this is a lot more significant, can we prove that these fungi are responsible for the pathological changes in the areas of the brain? More to be revealed…

Ruth Alonsoa,1, Diana Pisaa,1, Ana M. Fernández-Fernándeza, Alberto Rábanob, Luis Carrascoa

A B S T R A C T

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 pa-
tients. 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 neuro-
pathological observations of this disease, such as neuroinflammation and elevated chitinase levels, and could
help to implement appropriate therapies.

Dr. Raymond Oenbrink