2026-06-02T09:05:57Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/205892026-02-03T12:05:46Zcom_10630_2254col_10630_37959

00925njm 22002777a 4500 dc Mejías-Ortega, Marina author Sánchez-Mejías, Elisabeth author Núñez-Díaz, Cristina author Trujillo-Estrada, Laura Isabel author Sánchez-Varo, Raquel María author Dávila-Cansino, José Carlos author Gutiérrez-Pérez, Antonia author 2020-12-16 Parenchymal microglia, the brain-resident immune cells capable of responding to damage and disease, has been postulated as a critical factor in the Alzheimer´s disease (AD) progression. Apart from microglia, CNS macrophages, (PVMs), are also involved in neurodegeneration. However, the implication of myeloid cells in the human pathology have not been determined yet. Here, we analyzed the phenotypic profile displayed by these damage associated myeloid cells in the frontal cortex of AD brains. For this purpose, immunohistochemistry and image analysis approaches have been carried out in postmortem samples from non-demented controls and AD cases. Frontal cortex of AD patients showed strong myeloid activation similar to that observed in amyloidogenic mice. Microglial cells of Braak V VI patients were observed forming clusters and exhibited, both plaque and interplaque damage-associated phenotype. Moreover, in these individuals the PVMs were localized in the parenchyma, predominantly located surrounding amyloid plaques. On the contrary, Braak II with mild amyloid pathology (CERAD B) cases presented only activated microglial cells, while, immunoreactivity of CD163 was absent.These strongly activated myeloid cells, could drive the AD pathology and, in consequence, could be implicated in the pathology progression.Taken together, these findings suggest the existence of two populations of myeloid cells associated with Aβ plaques in the frontal cortex in the advanced stages of the pathology and probably due to failures in the integrity of the blood-brain barrier. The differential contribution of these two myeloid populations to the pathogenesis of the disease remains to be elucidated. These results open the opportunity to design targeted therapies, not only to microglia, but also to the population of macrophages, in order to modulate amyloid pathology and provide a better understanding of the immunological mechanisms underlying AD progression. https://hdl.handle.net/10630/20589 Alzheimer, enfermedad de Sistema nervioso - Degeneración Coexistance of different myeloid populations in the frontal cortex of alzheimer's disease patients