Microglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer’s Disease
| Autor: | Marcella Catania, Emanuela Maderna, Bernardino Ghetti, Giuseppe Di Fede, Stefano Sorrentino, Giorgio Giaccone, R Ascari, Fabrizio Tagliavini |
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| Přispěvatelé: | Sorrentino, S, Ascari, R, Maderna, E, Catania, M, Ghetti, B, Tagliavini, F, Giaccone, G, Di Fede, G |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Chemokine
Innate immunity factor microglia chemokines Disease Catalysis Article neuroinflammation Inorganic Chemistry Pathogenesis lcsh:Chemistry Alzheimer Disease medicine Dementia Humans Physical and Theoretical Chemistry CXCL13 Cytokine Molecular Biology lcsh:QH301-705.5 Spectroscopy Neuroinflammation Aβ innate immunity factors Inflammation MMP Microglia biology Organic Chemistry Brain General Medicine medicine.disease Phenotype cytokines Computer Science Applications medicine.anatomical_structure lcsh:Biology (General) lcsh:QD1-999 biology.protein MMPs heterogeneity Neuroscience Alzheimer’s disease dementia |
| Zdroj: | International Journal of Molecular Sciences Volume 22 Issue 5 International Journal of Molecular Sciences, Vol 22, Iss 2780, p 2780 (2021) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms22052780 |
| Popis: | Alzheimer’s disease (AD) is increasingly recognized as a highly heterogeneous disorder occurring under distinct clinical and neuropathological phenotypes. Despite the molecular determinants of such variability not being well defined yet, microglial cells may play a key role in this process by releasing distinct pro- and/or anti-inflammatory cytokines, potentially affecting the expression of the disease. We carried out a neuropathological and biochemical analysis on a series of AD brain samples, gathering evidence about the heterogeneous involvement of microglia in AD. The neuropathological studies showed differences concerning morphology, density and distribution of microglial cells among AD brains. Biochemical investigations showed increased brain levels of IL-4, IL-6, IL-13, CCL17, MMP-7 and CXCL13 in AD in comparison with control subjects. The molecular profiling achieved by measuring the brain levels of 25 inflammatory factors known to be involved in neuroinflammation allowed a stratification of the AD patients in three distinct “neuroinflammatory clusters”. These findings strengthen the relevance of neuroinflammation in AD pathogenesis suggesting, in particular, that the differential involvement of neuroinflammatory molecules released by microglial cells during the development of the disease may contribute to modulate the characteristics and the severity of the neuropathological changes, driving—at least in part—the AD phenotypic diversity. |
| Databáze: | OpenAIRE |
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