Preprint / Version 1

How interconnections between the gut microbiome and the brain influence Alzheimer's disease susceptibility and progression

##article.authors##

  • Fiyin Olabiyi Polygence

DOI:

https://doi.org/10.58445/rars.2363

Keywords:

gut microbiome, Alzheimer's Disease, gut-brain axis

Abstract

Alzheimer's disease is a neurodegenerative disorder that causes memory decline over time. The human gut is colonized with millions of microscopic organisms that can communicate with the brain. Recently research has established a gut-brain axis between these two organs, and this communication link has been implicated in neurodegenerative diseases such as Alzheimer's disease. Given the mounting evidence that the gut-brain axis impacts Alzheimer’s disease progression, the gut brain-axis may also have therapeutic potential. In this review, we discuss recent research that highlights the impact of the gut microbiome on Alzheimer’s disease using mouse models and human fecal samples. We hope that increased knowledge of the gut-brain axis expands our understanding of Alzheimer's disease and leads to the advancement of future treatments. 



References

It, K., & KNOW, W. (1986). What is Alzheimer’s disease? N Engl] Med, 314, 964-973.

Understanding how your relationship may change. (n.d.). Alzheimer Society of Canada. Retrieved December 26, 2024, from https://alzheimer.ca/en/help-support/i-have-friend-or-family-member-who-lives-dementia/understanding-how-your-relationship

Gaugler, J. E., Yu, F., Davila, H. W., & Shippee, T. (2014). Alzheimer's disease and nursing homes. Health affairs (Project Hope), 33(4), 650–657. https://doi.org/10.1377/hlthaff.2013.1268

Alzheimer's disease facts and figures. (2024). Alzheimer's & dementia : the journal of the Alzheimer's Association, 20(5), 3708–3821. https://d oi.org/10.1002/alz.13809

O'Brien, R. J., & Wong, P. C. (2011). Amyloid precursor protein processing and Alzheimer's disease. Annual review of neuroscience, 34, 185–204. https://doi.org/10.1146/annurev-neuro-061010-113613

What Happens to the Brain in Alzheimer’s Disease? (2024, January 19). National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease

Zhang, H., Jiang, X., Ma, L., Wei, W., Li, Z., Chang, S., Wen, J., Sun, J., & Li, H. (2022). Role of Aβ in Alzheimer’s-related synaptic dysfunction. Frontiers in Cell and Developmental Biology, 10. https://doi.org/10.3389/fcell.2022.964075

Kinney, J. W., Bemiller, S. M., Murtishaw, A. S., Leisgang, A. M., Salazar, A. M., & Lamb, B. T. (2018). Inflammation as a central mechanism in Alzheimer’s disease. Alzheimer’s & Dementia (New York, N. Y.), 4, 575–590. https://doi.org/10.1016/j.trci.2018.06.014

Wang, W.-Y., Tan, M.-S., Yu, J.-T., & Tan, L. (2015). Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Annals of Translational Medicine, 3(10), 136–136. https://doi.org/10.3978/j.issn.2305-5839.2015.03.49

Zhang, H., Wei, W., Zhao, M., Ma, L., Jiang, X., Pei, H., Cao, Y., & Li, H. (2021). Interaction between Aβ and Tau in the Pathogenesis of Alzheimer’s Disease. International Journal of Biological Sciences, 17(9), 2181–2192. https://doi.org/10.7150/ijbs.57078

Avila, J., Lucas, J. J., Pérez, M., & Hernández, F. (2004). Role of Tau Protein in Both Physiological and Pathological Conditions. Physiological Reviews, 84(2), 361–384. https://doi.org/10.1152/physrev.00024.2003

Tau Protein and Alzheimer’s Disease: What’s the Connection? | BrightFocus Foundation. (n.d.). https://www.brightfocus.org/alzheimers/article/tau-protein-and-alzheimers-disease-whats-connection

Zhang, H., Cao, Y., Ma, L., Wei, Y., & Li, H. (2021). Possible Mechanisms of Tau Spread and Toxicity in Alzheimer’s Disease. Frontiers in Cell and Developmental Biology, 9, 707268. https://doi.org/10.3389/fcell.2021.707268

Cummings, J. (2023). Anti-Amyloid Monoclonal Antibodies are Transformative Treatments that Redefine Alzheimer’s Disease Therapeutics. Drugs, 83(7), 569–576. https://doi.org/10.1007/s40265-023-01858-9

Alzheimer's Association (2024) (N.d.). https://www.alz.org/alzheimers-dementia/treatments/medications-for-memory#Types%20of%20drugs

How Alzheimer’s medicines help manage symptoms. (n.d.). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048103

Cryan, J. F., O’Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., Guzzetta, K. E., Jaggar, M., Long-Smith, C. M., Lyte, J. M., Martin, J. A., Molinero-Perez, A., Moloney, G., Morelli, E., Morillas, E., … Dinan, T. G. (2019). The Microbiota-Gut-Brain Axis. Physiological Reviews, 99(4), 1877–2013. https://doi.org/10.1152/physrev.00018.2018

Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. The Biochemical Journal, 474(11), 1823–1836. https://doi.org/10.1042/BCJ20160510

Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. BMJ, 361, k2179. https://doi.org/10.1136/bmj.k2179

Transgenic Mice. (n.d.). Charles River. https://www.criver.com/products-services/research-models-services/genetically-engineered-model-services/transgenic-mouse-rat-model-creation/transgenic-mice

Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. | ALZFORUM. (2002, May 21). Alzforum.org. https://www.alzforum.org/papers/accelerated-alzheimer-type-phenotype-transgenic-mice-carrying-both-mutant-amyloid-precursor

Tai, L. M., Maldonado Weng, J., LaDu, M. J., & Brady, S. T. (2021). Relevance of transgenic mouse models for Alzheimer’s disease. Progress in Molecular Biology and Translational Science, 177, 1–48. https://doi.org/10.1016/bs.pmbts.2020.07.007

Liu, Y., Li, H., Wang, X., Huang, J., Zhao, D., Tan, Y., Zhang, Z., Zhang, Z., Zhu, L., Wu, B., Chen, Z., & Peng, W. (2023). Anti-Alzheimer's molecular mechanism of icariin: insights from gut microbiota, metabolomics, and network pharmacology. Journal of Translational Medicine, 21(1), 277. https://doi.org/10.1186/s12967-023-04137-z

Traini, C., Bulli, I., Sarti, G., Morecchiato, F., Coppi, M., Rossolini, G. M., Di Pilato, V., & Vannucchi, M. G. (2024). Amelioration of Serum Aβ Levels and Cognitive Impairment in APPPS1 Transgenic Mice Following Symbiotic Administration. Nutrients, 16(15), 2381. https://doi.org/10.3390/nu16152381

Lu, J., Zhang, S., Huang, Y., Qian, J., Tan, B., Qian, X., Zhuang, J., Zou, X., Li, Y., & Yan, F. (2022). Periodontitis-related salivary microbiota aggravates Alzheimer’s disease via gut-brain axis crosstalk. Gut Microbes, 14(1), 2126272. https://doi.org/10.1080/19490976.2022.2126272

xFAD (C57BL6) | ALZFORUM. (n.d.). www.alzforum.org. https://www.alzforum.org/research-models/5xfad-c57bl6

Guilherme, M. dos S., Nguyen, V. T. T., Reinhardt, C., & Endres, K. (2021). Impact of Gut Microbiome Manipulation in 5xFAD Mice on Alzheimer’s Disease-Like Pathology. Microorganisms, 9(4), 815. https://doi.org/10.3390/microorganisms9040815

Kim, H., Lee, E., Park, M., Min, K., Diep, Y. N., Kim, J., Ahn, H., Lee, E., Kim, S., Kim, Y., Kang, Y. J., Jung, J. H., Byun, M. S., Joo, Y., Jeong, C., Lee, D. Y., Cho, H., Park, H., & Kim, T. (2024). Microbiome-derived indole-3-lactic acid reduces amyloidopathy through aryl-hydrocarbon receptor activation. Brain, Behavior, and Immunity, 122, 568–582. https://doi.org/10.1016/j.bbi.2024.08.051

Ph.D, D. S. P. (2018, July 24). What is Multiomics? News-Medical. https://www.news-medical.net/life-sciences/What-is-Multiomics.aspx

Mezö, C., Dokalis, N., Mossad, O., Staszewski, O., Neuber, J., Yilmaz, B., Schnepf, D., de Agüero, M. G., Ganal-Vonarburg, S. C., Macpherson, A. J., Meyer-Luehmann, M., Staeheli, P., Blank, T., Prinz, M., & Erny, D. (2020). Different effects of constitutive and induced microbiota modulation on microglia in a mouse model of Alzheimer’s disease. Acta Neuropathologica Communications, 8(1), 119. https://doi.org/10.1186/s40478-020-00988-5

The Future of Medicine Is in Your Poop. (2024). NIST. https://www.nist.gov/health/future-medicine-your-poop

Schoch, C. L., Seifert, K. A., Huhndorf, S., Robert, V., Spouge, J. L., Levesque, C. A., Chen, W., Fungal Barcoding Consortium, Fungal Barcoding Consortium Author List, Bolchacova, E., Voigt, K., Crous, P. W., Miller, A. N., Wingfield, M. J., Aime, M. C., An, K.-D., Bai, F.-Y., Barreto, R. W., Begerow, D., … Schindel, D. (2012). Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proceedings of the National Academy of Sciences, 109(16), 6241–6246. https://doi.org/10.1073/pnas.1117018109

Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., Bendlin, B. B., & Rey, F. E. (2017). Gut microbiome alterations in Alzheimer’s disease. Scientific Reports, 7(1), 13537. https://doi.org/10.1038/s41598-017-13601-y

Jung, J. H., Kim, G., Byun, M. S., Lee, J. H., Yi, D., Park, H., Lee, D. Y., & KBASE Research Group. (2022). Gut microbiome alterations in preclinical Alzheimer’s disease. PloS One, 17(11), e0278276. https://doi.org/10.1371/journal.pone.0278276

Ferreiro, A. L., Choi, J., Ryou, J., Newcomer, E. P., Thompson, R., Bollinger, R. M., Hall-Moore, C., Ndao, I. M., Sax, L., Benzinger, T. L. S., Stark, S. L., Holtzman, D. M., Fagan, A. M., Schindler, S. E., Cruchaga, C., Butt, O. H., Morris, J. C., Tarr, P. I., Ances, B. M., & Dantas, G. (2023). Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease. Science Translational Medicine, 15(700), eabo2984. https://doi.org/10.1126/scitranslmed.abo2984

Van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., Froelich, L., Katayama, S., Sabbagh, M., Vellas, B., Watson, D., Dhadda, S., Irizarry, M., Kramer, L. D., & Iwatsubo, T. (2023). Lecanemab in Early Alzheimer’s Disease. New England Journal of Medicine, 388(1), 9–21. https://doi.org/10.1056/NEJMoa2212948

Sims, J. R., Zimmer, J. A., Evans, C. D., Lu, M., Ardayfio, P., Sparks, J., Wessels, A. M., Shcherbinin, S., Wang, H., Monkul Nery, E. S., Collins, E. C., Solomon, P., Salloway, S., Apostolova, L. G., Hansson, O., Ritchie, C., Brooks, D. A., Mintun, M., Skovronsky, D. M., & TRAILBLAZER-ALZ 2 Investigators. (2023). Donanemab in Early Symptomatic Alzheimer Disease: The TRAILBLAZER-ALZ 2 Randomized Clinical Trial. JAMA, 330(6), 512–527. https://doi.org/10.1001/jama.2023.13239

Baas, P. W., Rao, A. N., Matamoros, A. J., & Leo, L. (2016). Stability properties of neuronal microtubules. Cytoskeleton (Hoboken, N.J.), 73(9), 442–460. https://doi.org/10.1002/cm.21286

Sasaguri, H., Nilsson, P., Hashimoto, S., Nagata, K., Saito, T., De Strooper, B., Hardy, J., Vassar, R., Winblad, B., & Saido, T. C. (2017). APP mouse models for Alzheimer’s disease preclinical studies. The EMBO Journal, 36(17), 2473–2487. https://doi.org/10.15252/embj.201797397

Lopes van den Broek, S., Sehlin, D., Andersen, J. V., Aldana, B. I., Beschörner, N., Nedergaard, M., Knudsen, G. M., Syvänen, S., & Herth, M. M. (2022). The Alzheimer’s disease 5xFAD mouse model is best suited to investigate pretargeted imaging approaches beyond the blood-brain barrier. Frontiers in Nuclear Medicine, 2. https://doi.org/10.3389/fnume.2022.1001722

Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., Berry, R., & Vassar, R. (2006). Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer’s Disease Mutations: Potential Factors in Amyloid Plaque Formation. The Journal of Neuroscience, 26(40), 10129. https://doi.org/10.1523/JNEUROSCI.1202-06.2000

How Alzheimer’s medicines help manage symptoms. (n.d.). Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers/art-20048103

Drummond, E., & Wisniewski, T. (2017). Alzheimer’s disease: experimental models and reality. Acta Neuropathologica, 133(2), 155–175. https://doi.org/10.1007/s00401-016-1662-x

Liu, K. Y., Walsh, S., Brayne, C., Merrick, R., Richard, E., & Howard, R. (2023). Evaluation of clinical benefits of treatments for Alzheimer’s disease. The Lancet. Healthy Longevity, 4(11), e645–e651. https://doi.org/10.1016/S2666-7568(23)00193-9

Downloads

Posted

2025-03-24

Categories