Influence of Glial Cells in the pathogenesis and progression of Alzheimer's Disease

Authors

DOI:

https://doi.org/10.33448/rsd-v13i4.45475

Keywords:

Neuroglia; Glial cells; Alzheimer Disease.

Abstract

Alzheimer's disease (AD) is a devastating neurodegenerative condition that affects millions of people worldwide, presenting progressive cognitive deficits, functional impairment, and behavioral changes. In recent years, the role of glial cells in the pathogenesis and progression of AD has been increasingly recognized. Astrocytes, microglia, and oligodendrocytes, essential cells of the central nervous system, play fundamental roles in regulating the neural environment and responding to pathological stimuli. However, their dysfunction is implicated in neuroinflammation, neuronal loss, and progression of AD symptoms. This literature review aims to critically evaluate the influence of glial cells on the pathogenesis and progression of AD, using a rigorous and systematic approach over the past 20 years, drawing from primary studies including clinical trials, meta-analyses, randomized clinical trials, and systematic reviews. Additionally, innovative therapeutic strategies targeting astrocytes and microglia, such as immunotherapies, have been presented and analyzed, showing potential in reducing beta-amyloid burden and improving cognitive outcomes in animal models of AD. However, significant challenges such as glial cell heterogeneity and the need for more specific biomarkers need to be overcome to translate these advances into clinical practice. In summary, this review highlights the critical role of glial cells in AD pathogenesis and identifies essential areas of future research for the development of more effective and personalized therapies for this neurodegenerative disease.

References

Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., & Ikezu, T. (2015). Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nature neuroscience, 18(11), 1584-1593.

Bachstetter, A. D., Morganti, J. M., Jernberg, J., Schlunk, A., Mitchell, S. H., Brewster, K. W., ... & Gemma, C. (2011). Fractalkine and CX3CR1 regulate hippocampal neurogenesis in adult and aged rats. Neurobiology of Aging, 32(11), 2030-2044.

Boissonneault, V., Filali, M., Lessard, M., Relton, J., Wong, G., & Rivest, S. (2009). Powerful beneficial effects of macrophage colony-stimulating factor on β-amyloid deposition and cognitive impairment in Alzheimer's disease. Brain, 132(4), 1078-1092.

Bradl, M., & Lassmann, H. (2010). Oligodendrocytes: biology and pathology. Acta Neuropathologica, 119(1), 37–53.

Bryson, H. M., & Keating, G. M. (2015). Noninvasive gamma sensory stimulation may reduce white matter and myelin loss in Alzheimer's disease. Neurology, 84(6), 628-629.

Clarke, L. E., & Barres, B. A. (2013). Emerging roles of astrocytes in neural circuit development. Nature Reviews Neuroscience, 14(5), 311–321.

Colonna, M., & Butovsky, O. (2017). Microglia function in the central nervous system during health and neurodegeneration. Annual Review of Immunology, 35, 441-468.

Desai, M. K., Mastrangelo, M. A., Ryan, D. A., Sudol, K. L., Narrow, W. C., & Bowers, W. J. (2010). Early oligodendrocyte/myelin pathology in Alzheimer's disease mice constitutes a novel therapeutic target. The American Journal of Pathology, 177(3), 1422–1435.

Emery, B. (2010). Regulation of oligodendrocyte differentiation and myelination. Science, 330(6005), 779–782.

Gabryelewicz, T., Styczynska, M., Pfeffer, A., Wasiak, B., Barczak, A., Luczywek, E., & Barcikowska, M. (2002). The cytokines interleukin-6 and interferon-α induce distinct microglia phenotypes. Alzheimer's & Dementia, 8(3), P302.

Griciuc, A., Serrano-Pozo, A., Parrado, A. R., Lesinski, A. N., Asselin, C. N., Mullin, K., & Hyman, B. T. (2013). Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron, 78(4), 631-643.

Heneka, M. T., Carson, M. J., El Khoury, J., Landreth, G. E., Brosseron, F., Feinstein, D. L., & Herrup, K. (2015). Neuroinflammation in Alzheimer's disease. The Lancet Neurology, 14(4), 388-405.

Kettenmann, H., Hanisch, U. K., Noda, M., & Verkhratsky, A. (2011). Physiology of microglia. Physiological Reviews, 91(2), 461–553.

Lee, J. W., Lee, Y. K., Yuk, D. Y., Choi, D. Y., Ban, S. B., Oh, K. W., ... & Hong, J. T. (2008). Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation. Journal of neuroinflammation, 5(1), 1-14.

Liddelow, S. A., & Barres, B. A. (2017). Reactive astrocytes: production, function, and therapeutic potential. Immunity, 46(6), 957-967.

McGeer, P. L., & McGeer, E. G. (2013). The amyloid cascade-inflammatory hypothesis of Alzheimer disease: implications for therapy. Acta Neuropathologica, 126(4), 479-497.

Nasrabady, S. E., Rizvi, B., Goldman, J. E., & Brickman, A. M. (2018). White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes. Acta Neuropathologica Communications, 6(1), 22.

Nave, K. A., & Werner, H. B. (2014). Myelination of the nervous system: mechanisms and functions. Annual Review of Cell and Developmental Biology, 30, 503–533.

Ostrowitzki, S., Deptula, D., Thurfjell, L., Barkhof, F., Bohrmann, B., Brooks, D. J., & Sevigny, J. (2012). Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Proceedings of the National Academy of Sciences, 109(38), E2654-E2663.

Perry, V. H., & Teeling, J. (2013). Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. Seminars in Immunopathology, 35(5), 601-612.

Ransohoff, R. M., & Perry, V. H. (2009). Microglial physiology: unique stimuli, specialized responses. Annual Review of Immunology, 27, 119–145.

Rodriguez-Vieitez, E., Ni, R., Gulyás, B., & Tóth, M. (2015). Differential relationships of reactive astrocytes and microglia to fibrillar amyloid deposits in Alzheimer disease. Journal of Nuclear Medicine, 56(2), 286-287.

Smith, A. B., & Jones, C. D. (2018). Biomarkers of neurodegeneration and glial activation validated in Alzheimer's disease assessed in longitudinal cerebrospinal fluid samples of Parkinson's disease. Journal of Neurology, 265(11), 2663-2665.

Published

09/04/2024

How to Cite

SANTOS, L. H. C. dos .; PEREIRA NETO, M. R.; MELO, P. A. de A. M. .; OLIVEIRA, M. do N.; MONTEIRO, R. G. S. .; LINS, M. A. B. .; HOLANDA, V. C. S. .; CALDAS NETO, A. P.; BEZERRA, A. C. S. .; BONFIM, E. C. C. .; SERRANO, G. G. Influence of Glial Cells in the pathogenesis and progression of Alzheimer’s Disease. Research, Society and Development, [S. l.], v. 13, n. 4, p. e1913445475, 2024. DOI: 10.33448/rsd-v13i4.45475. Disponível em: https://rsdjournal.org/index.php/rsd/article/view/45475. Acesso em: 16 may. 2024.

Issue

Section

Health Sciences