RT Conference Proceedings
T1 Coexistance of different myeloid populations in the frontal cortex of alzheimer's disease patients
A1 Mejías-Ortega, Marina
A1 Sánchez-Mejías, Elisabeth
A1 Núñez-Díaz, Cristina
A1 Trujillo-Estrada, Laura Isabel
A1 Sánchez-Varo, Raquel María
A1 Dávila-Cansino, José Carlos
A1 Gutiérrez-Pérez, Antonia
K1 Alzheimer, enfermedad de
K1 Sistema nervioso - Degeneración
AB 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-associatedphenotype. 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 thepathology 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.
YR 2020
FD 2020-12-16
LK https://hdl.handle.net/10630/20589
UL https://hdl.handle.net/10630/20589
LA eng
NO Supported by PI18/01557 (AG) and PI18/01556 (JV) grants from ISCiii of Spain and Junta de Andalucia UMA18-FEDERJA211 (to AG), all co-financed by FEDER funds from European Union. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 20 ene 2026