Microglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer’s Disease

dc.contributor.authorSorrentino, Stefano
dc.contributor.authorAscari, Roberto
dc.contributor.authorMaderna, Emanuela
dc.contributor.authorCatania, Marcella
dc.contributor.authorGhetti, Bernardino
dc.contributor.authorTagliavini, Fabrizio
dc.contributor.authorGiaccone, Giorgio
dc.contributor.authorDi Fede, Giuseppe
dc.contributor.departmentPathology and Laboratory Medicine, School of Medicineen_US
dc.date.accessioned2022-06-15T17:23:06Z
dc.date.available2022-06-15T17:23:06Z
dc.date.issued2021-03-09
dc.description.abstractAlzheimer'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.en_US
dc.eprint.versionFinal published versionen_US
dc.identifier.citationSorrentino S, Ascari R, Maderna E, et al. Microglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer's Disease. Int J Mol Sci. 2021;22(5):2780. Published 2021 Mar 9. doi:10.3390/ijms22052780en_US
dc.identifier.urihttps://hdl.handle.net/1805/29351
dc.language.isoen_USen_US
dc.publisherMDPIen_US
dc.relation.isversionof10.3390/ijms22052780en_US
dc.relation.journalInternational Journal of Molecular Sciencesen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.sourcePMCen_US
dc.subjectAlzheimer’s diseaseen_US
dc.subjectChemokinesen_US
dc.subjectCytokinesen_US
dc.subjectDementiaen_US
dc.subjectHeterogeneityen_US
dc.subjectInnate immunity factorsen_US
dc.subjectMicrogliaen_US
dc.subjectNeuroinflammationen_US
dc.titleMicroglial Heterogeneity and Its Potential Role in Driving Phenotypic Diversity of Alzheimer’s Diseaseen_US
dc.typeArticleen_US
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