A closer look at the mycobiome in Alzheimer's disease: Fungal species, pathogenesis and transmission.

Candida spp., Malassezia spp., Cladosporium spp. and Alternaria spp. are among the most common fungi detected in the brain of patients with Alzheimer's disease (AD). These fungi are opportunistic organisms, where they often cause infection among immunocompromised patients. Coincidentally, these fungi can reach the brain and cause fungal meningitis. In general, they enter the brain via systemic infection due to disrupted epithelial barrier from skin and gut colonization. Once it reaches the brain, Candida species has been postulated to induce fungal glial granulomas with amyloid precursor protein (APP) accumulated inside. Cleavage of APP can lead to the production of amyloid beta (Aβ). Malassezia species can lead to neuroinflammation via activating helper T-cell (Th) 1 and Th17 immune response. Besides that, the pathogenesis of Cladosporium species and Alternaria species in AD remains unknown, but it could be related to the neuroinflammation. These two fungal species may have involved in acetylcholinesterase (AChE) inhibitor production in the brain. All these four fungi can be detected at the same time in the brain, which contribute to chronic neuroinflammation and neurodegeneration in the brain. This review hopes to shed some light in understanding the presence of fungi in the brain and their possible role in AD pathogenesis.