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dc.contributor.authorMejías-Ortega, Marina
dc.contributor.authorMuñoz-Castro, Clara
dc.contributor.authorSánchez-Mejías, Elisabeth 
dc.contributor.authorJiménez, Sebastián
dc.contributor.authorTrujillo-Estrada, Laura Isabel 
dc.contributor.authorVizuete, María Luisa
dc.contributor.authorVitorica Ferrández, Javier
dc.contributor.authorGutiérrez-Pérez, Antonia 
dc.date.accessioned2023-09-29T09:59:58Z
dc.date.available2023-09-29T09:59:58Z
dc.date.issued2023
dc.identifier.urihttps://hdl.handle.net/10630/27702
dc.description.abstractMicroglia, the brain-resident myeloid cells, play a major role in the immune responses of the nervous system and in the pathogenesis of Alzheimer's disease (AD). However, the presence of peripheral myeloid cells in the AD brains, and their contribution to disease progression, remain to be demonstrated. In this work, cellular and molecular approaches have been carried out in post-mortem hippocampal samples from patients with dementia (Braak V-VI) and age-matched asymptomatic cases (Braak II). Our study provides evidence that circulating monocytes infiltrate the AD brains. Our findings showed that a high proportion of demented individuals was associated with up-regulation of genes rarely expressed by microglial cells and abundant in monocytes-derived cells (MDC), among which stands the scavenger receptor Cd163. These Cd163-positive MDC invaded the brain parenchyma, acquired a microglial-like morphology, and were located in close proximity to blood vessels. These cells infiltrated the nearby amyloid plaques contributing to plaque-associated myeloid cell heterogeneity. Besides, asymptomatic individuals with high amyloid pathology, showed no signs of MDC brain infiltration or plaque invasion. The MDC infiltration was associated with the progression and severity of AD pathology. These results reveal the co-existence of distinct myeloid populations associated with amyloid plaques during disease progression, as well their region-specific contribution to neuroimmune protection. The recruitment of monocytes could be a consequence rather than the cause of the severity of the disease. Whether monocyte infiltration is beneficial or detrimental to AD pathology remains to be fully elucidated. These findings open the opportunity to design targeted therapies, not only to microglia, but also to peripheral immune cell population to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying AD progression.es_ES
dc.description.sponsorshipSupported by ISCiii grants (PI21-0915 (to AG),PI21-00914 (to JV) co-financed by FEDER funds from European Union, by Junta de Andalucia grants P18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014-2020, and by grant PPIT.UMA.B1-2019-07 (to ESM). Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.es_ES
dc.language.isospaes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectAlzheimer, Enfermedad dees_ES
dc.subjectMonocitoses_ES
dc.subjectCerebro - Enfermedadeses_ES
dc.subject.otherAlzheimeres_ES
dc.subject.otherMicrogliaes_ES
dc.subject.otherMonocyteses_ES
dc.subject.otherNeuroinflammationes_ES
dc.subject.otherHuman braines_ES
dc.subject.otherNeurodegenerationes_ES
dc.titleMonocyte-derived cells invade amyloid plaques in human alzheimer’s disease hippocampus.es_ES
dc.typeinfo:eu-repo/semantics/conferenceObjectes_ES
dc.centroFacultad de Cienciases_ES
dc.relation.eventtitleInternational Congress on Neurodegenerative Diseaseses_ES
dc.relation.eventplaceMálaga (Spain)es_ES
dc.relation.eventdateSeptiembre 2023es_ES


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