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Alzheimer's disease (AD) is a progressive neurodegenerative condition that leads to dementia mainly among the elderly. Despite numerous efforts from many laboratories, the precise etiology of AD remains elusive. We have analyzed the existence of fungal infection in AD patients. A number of tests have been carried out in blood serum, including the detection of antibodies against several yeast species and fungal proteins, and also the presence of fungal (1,3)-β-glucan. Results from this analysis indicate that disseminated fungal infection can be detected in the majority of AD patients tested. We show that fungal proteins can be detected in cerebrospinal fluid using a slot-blot assay with different anti-fungal antibodies. In addition, proteomic analysis provides strong evidence for the existence of fungal proteins in brain samples Furthermore, amplification of fungal DNA by PCR followed by sequencing distinguishes several fungal species. PCR analysis of these samples reveals a variety of amplified DNA fragments that are dependent on the patient and the tissue tested. DNA sequencing of these fragments demonstrates that several fungal species can be found in brain samples. Collectively, these various assays show that fungal macromolecules can be detected in brain from AD patients and direct visualization of fungal infection in brain tissue provides compelling evidence for the presence for yeast-shaped cells and fungal hyphae. To our knowledge, these findings represent the first evidence that fungal infection is detectable in blood and brain samples from AD patients. The possibility that this may contribute to the etiological cause of AD is proposed.
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