A closer look at the mycobiome in Alzheimer’s disease: Fungal species, pathogenesis and transmission
Abstract
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.
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These findings have been further supported by immunohistochemistry and next generation sequencing analysis of AD brain tissues, collectively suggesting a strong association between fungal infections and AD.
“These findings have been further supported by immunohistochemistry and next generation sequencing analysis of AD brain tissues, collectively suggesting a strong association between fungal infections and AD [88].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [88]
Human chitinases and chitinases-like proteins are among the most upregulated proteins detected in the plasma and CSF of AD patients, with levels often correlating with the disease progression.
“Intriguingly, human chitinases and chitinases-like proteins are among the most upregulated proteins detected in the plasma and CSF of AD patients, with levels often correlating with the disease progression [88].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [88]
Amyloid precursor protein (APP) and APP-derived Aβ peptides have been found to accumulate at the periphery of these glial nodules, potentially contributing to antifungal immune responses.
“Also, amyloid precursor protein (APP) and APP-derived Aβ peptides have been found to accumulate at the periphery of these glial nodules, potentially contributing to antifungal immune responses [88].”
From What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease? (2025) · cites this paper as [88]
Cites
Nichols, E., Szoeke, C. E. I., Vollset, S. E., Abbasi, N., Abd-Allah, F., Abdela, J., Aichour, M. T. E., Akinyemi, R. O., Alahdab, F., Asgedom, S. W., et al. (2019) · The Lancet Neurology · doi:10.1016/s1474-4422(18)30403-4 · Cited by 2,412 · see citing works
Inflammation as a central mechanism in Alzheimer's disease
Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.06.014 · Cited by 2,253 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Topographic diversity of fungal and bacterial communities in human skin
NIH Intramural Sequencing Center Comparative Sequencing Program, Findley, K., Oh, J., Yang, J., Conlan, S., Deming, C., Meyer, J. A., Schoenfeld, D., Nomicos, E., Park, M., et al. (2013) · Nature · doi:10.1038/nature12171 · Cited by 1,206 · see citing works
Characterization of the oral fungal microbiome (mycobiome) in healthy individuals
Ghannoum, M. A., Jurevic, R. J., Mukherjee, P. K., Cui, F., Sikaroodi, M., Naqvi, A., & Gillevet, P. M. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000713 · Cited by 1,150 · see citing works
Current understanding of Alzheimer’s disease diagnosis and treatment
Weller, J., & Budson, A. (2018) · F1000Research · doi:10.12688/f1000research.14506.1 · Cited by 1,083 · see citing works
Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis
Iliev, I. D., Funari, V. A., Taylor, K. D., Nguyen, Q., Reyes, C. N., Strom, S. P., Brown, J., Becker, C. A., Fleshner, P. R., Dubinsky, M., et al. (2012) · Science · doi:10.1126/science.1221789 · Cited by 1,073 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · cited 1× · see citing works
“…AD at younger age, whereas those with low baseline function and slower mitochondrial decline rate will develop the AD symptoms at intermediate ages (Swerdlow et al., 2014) Calcium homeostasis hypothesis Dysregulation of neuronal calcium (Ca2+) homeostasis due to ageing can induce synaptic deficits…”
BackgroundHistory and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723 · see citing works
Drug treatments in Alzheimer’s disease
Briggs, R., Kennelly, S. P., & O’Neill, D. (2016) · Clinical Medicine · doi:10.7861/clinmedicine.16-3-247 · Cited by 571 · see citing works
Activation of HIF-1α and LL-37 by commensal bacteria inhibits Candida albicans colonization
Fan, D., Coughlin, L. A., Neubauer, M. M., Kim, J., Kim, M. S., Zhan, X., Simms-Waldrip, T. R., Xie, Y., Hooper, L. V., & Koh, A. Y. (2015) · Nature Medicine · doi:10.1038/nm.3871 · Cited by 426 · cited 1× · see citing works
“1 Koh, A. Y., Köhler, J. R., Coggshall, K. T., Van Rooijen, N., & Pier, G. B. (2008). Mucosal damage and neutropenia are required for Candida albicans dissemination.”
Ilievski, V., Zuchowska, P. K., Green, S. J., Toth, P. T., Ragozzino, M. E., Le, K., Aljewari, H. W., O’Brien-Simpson, N. M., Reynolds, E. C., & Watanabe, K. (2018) · PLOS ONE · doi:10.1371/journal.pone.0204941 · Cited by 372 · see citing works
Kim, Y.-G., Udayanga, K. G. S., Totsuka, N., Weinberg, J. B., Núñez, G., & Shibuya, A. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2013.12.010 · Cited by 366 · see citing works
Vulvovaginal Candidiasis: A Current Understanding and Burning Questions
Willems, H. M. E., Ahmed, S. S., Liu, J., Xu, Z., & Peters, B. M. (2020) · Journal of Fungi · doi:10.3390/jof6010027 · Cited by 357 · see citing works
Zhang, J., Yu, C., Zhang, X., Chen, H., Dong, J., Lu, W., Song, Z., & Zhou, W. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1052-x · Cited by 297 · see citing works
Sparber, F., De Gregorio, C., Steckholzer, S., Ferreira, F. M., Dolowschiak, T., Ruchti, F., Kirchner, F. R., Mertens, S., Prinz, I., Joller, N., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.02.002 · Cited by 255 · see citing works
Suh, J., Choi, S. H., Romano, D. M., Gannon, M. A., Lesinski, A. N., Kim, D. Y., & Tanzi, R. E. (2013) · Neuron · doi:10.1016/j.neuron.2013.08.035 · Cited by 217 · see citing works
Beydoun, M. A., Beydoun, H. A., Hossain, S., El-Hajj, Z. W., Weiss, J., & Zonderman, A. B. (2020) · Journal of Alzheimer's Disease · doi:10.3233/jad-200064 · Cited by 201 · see citing works
Association between genetic traits for immune-mediated diseases and Alzheimer disease
Yokoyama, J. S., Wang, Y., Schork, A. J., Thompson, W. K., Karch, C. M., Cruchaga, C., McEvoy, L. K., Witoelar, A., Chen, C.-H., Holland, D., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0150 · Cited by 176 · see citing works
Pomilio, C., Gorojod, R. M., Riudavets, M., Vinuesa, A., Presa, J., Gregosa, A., Bentivegna, M., Alaimo, A., Alcon, S. P., Sevlever, G., et al. (2020) · GeroScience · doi:10.1007/s11357-020-00161-9 · Cited by 109 · see citing works
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What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
Brutkiewicz, R. R., Cao, W., Morgan, D., Reis, R. S. D., Suryadevara, V., Willette, A. A., Willette, S. A., Wyatt-Johnson, S. K., & Duggan, M. R. (2025) · Trends in Neurosciences · doi:10.1016/j.tins.2025.05.009 · Cited by 3 · see citing works
- Authors
- Phuna, Z. X., & Madhavan, P.
- Affiliations
- Taylor's University (MY)
- Corresponding author
- Madhavan, Priya
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2022-02-08
- Volume
- 55
- Issue
- 5
- Pages
- 1291-1321
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W4205186849
- Cited by
- 41
- References
- 20
- Citations by year
- 2026: 12 · 2025: 10 · 2024: 12 · 2023: 5 · 2022: 2
- FWCI
- 1.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Taylor’s University (TUFR/2017/002/04)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, fungal communities, Candida, Malassezia, Cladosporium, Alternaria, fungal meningitis, amyloid precursor protein, amyloid-beta, neuroinflammation, Th17 response, acetylcholinesterase inhibitors, neurodegeneration, opportunistic fungal pathogens
- MeSH terms
- Mycobiome, Acetylcholinesterase, Alzheimer Disease, Humans, Amyloid beta-Peptides, Amyloid beta-Protein Precursor
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