The Role of Microglia in Alzheimer's Disease
Aanandita Mahavadi¹, Arushi Gupta², Jalyn Huang²#
¹ Mountain House High School
² Irvine High School
#Advisor
ABSTRACT
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is the leading cause of dementia worldwide. It is marked by memory loss, behavioral changes, and cognitive decline, driven by the accumulation of amyloid beta plaques and tau tangles in the brain. While these specific protein abnormalities have been the focus of research, increasing evidence has shown that chronic neuroinflammation also plays a big role in the disease's progression. Microglia is a resident immune cell in the central nervous system and a key contributor to the process. Although it normally protects the brain, microglia shifts into an overactive state in Alzheimer's as it releases pro-inflammatory molecules that damage neurons and increase symptoms. Genetic factors like mutations in TREM2 and CD33 can further influence microglial function, linking these cells to the onset and progression of Alzheimer's. . Current treatments remain limited to symptom management as there is no permanent cure to Alzheimer's Although emerging therapies are starting to look into ways to regulate microglial activity, as they aim to restore microglia's protective role in the brain without harming too much. This paper will review the role of microglia in Alzheimer's pathology and highlight their potential as a promising target for future therapies.
References
Leng, F., & Edison, P. (2020). Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here? Nature Reviews Neurology, 17(3). https://doi.org/10.1038/s41582-020-00435-y
Melika AmeliMojarad, & Mandana AmeliMojarad. (2024). The neuroinflammatory role of microglia in Alzheimer’s disease and their associated therapeutic targets. CNS Neuroscience & Therapeutics, 30(7). https://doi.org/10.1111/cns.14856
Miao, J., Ma, H., Yang, Y., Liao, Y., Chen, L., Zheng, J., Yu, M., & Lan, J. (2023). Microglia in Alzheimer’s disease: pathogenesis, mechanisms, and therapeutic potentials. Frontiers in Aging Neuroscience, 15(15). https://doi.org/10.3389/fnagi.2023.1201982
Gouras, G. K., Olsson, T. T., & Hansson, O. (2014). β-amyloid Peptides and Amyloid Plaques in Alzheimer’s Disease. Neurotherapeutics, 12(1), 3–11. https://doi.org/10.1007/s13311-014-0313-y
Hansen, D. V., Hanson, J. E., & Sheng, M. (2017). Microglia in Alzheimer’s disease. Journal of Cell Biology, 217(2), 459–472. https://doi.org/10.1083/jcb.201709069
National Institute on Aging. (2024, January 19). What happens to the brain in Alzheimer's disease? National Institute on Aging. https://www.nia.nih.gov/health/alzheimers-causes-and-risk-factors/what-happens-brain-alzheimers-disease
Colonna, M., & Butovsky, O. (2017). Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annual Review of Immunology, 35(1), 441–468. https://doi.org/10.1146/annurev-immunol-051116-052358
Familial Alzheimer’s Disease. (2024). Memory and Aging Center. https://memory.ucsf.edu/genetics/familial-alzheimer-disease
How microglia contribute to Alzheimer’s disease. (n.d.). MIT News | Massachusetts Institute of Technology. https://news.mit.edu/2022/microglia-apoe4-alzheimers-0804
Qin, Q., Teng, Z., Liu, C., Li, Q., Yin, Y., & Tang, Y. (2021). TREM2, microglia, and Alzheimer’s disease. Mechanisms of Ageing and Development, 195, 111438. https://doi.org/10.1016/j.mad.2021.111438
Arcuri, C., Mecca, C., Bianchi, R., Giambanco, I., & Donato, R. (2017). The Pathophysiological Role of Microglia in Dynamic Surveillance, Phagocytosis and Structural Remodeling of the Developing CNS. Frontiers in Molecular Neuroscience, 10. https://doi.org/10.3389/fnmol.2017.00191
Wang, C., Zong, S., Cui, X., Wang, X., Wu, S., Wang, L., Liu, Y., & Lu, Z. (2023). The Effects of microglia-associated Neuroinflammation on Alzheimer’s Disease. Frontiers in Immunology, 14(1). https://doi.org/10.3389/fimmu.2023.1117172
Cosker, K., Mallach, A., Limaye, J., Piers, T. M., Staddon, J., Neame, S. J., Hardy, J., & Pocock,J. M. (2021). Microglial signalling pathway deficits associated with the patient derived R47H TREM2 variants linked to AD indicate inability to activate inflammasome. Scientific Reports, 11(1). https://doi.org/10.1038/s41598-021-91207-1
Gao, C., Jiang, J., Tan, Y., & Chen, S. (2023). Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduction and Targeted Therapy, 8(1), 1–37. https://doi.org/10.1038/s41392-023-01588-0
Ren, S., Yao, W., Tambini, M. D., Yin, T., Norris, K. A., & D’Adamio, L. (2020). Microglia TREM2R47H Alzheimer-linked variant enhances excitatory transmission and reduces LTP via increased TNF-α levels. ELife, 9. https://doi.org/10.7554/elife.57513
Guan, Y., Zhang, L., Wang, S., Deng, Y., Zhou, H., Chen, D., & Zhang, L. (2022). The role of microglia in Alzheimer’s disease and progress of treatment. Ibrain, 8(1), 37–47. https://doi.org/10.1002/ibra.12023
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., Itzkovitz, S., Colonna, M., Schwartz, M., & Amit, I. (2017). A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease. Cell, 169(7), 1276-1290.e17. https://doi.org/10.1016/j.cell.2017.05.018
Merighi, S., Nigro, M., Travagli, A., & Gessi, S. (2022). Microglia and Alzheimer’s Disease. International Journal of Molecular Sciences, 23(21), 12990. https://doi.org/10.3390/ijms232112990
