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Region‐specific microglial dynamics in the brain of Alzheimer's patients
Author(s) -
MejiasOrtega Marina,
SanchezMejias Elisabeth,
Navarro Victoria,
NuñezDiaz Cristina,
SanchezVaro Raquel,
JimenezMuñoz Sebastian,
Davila Jose Carlos,
Vitorica Javier,
Gutierrez Antonia
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.047410
Subject(s) - microglia , hippocampus , pathology , neuroscience , phenotype , temporal cortex , biology , neuroglia , cortex (anatomy) , alzheimer's disease , disease , medicine , central nervous system , inflammation , immunology , gene , genetics
Background The neuroinflammatory process involving particularly microglial cells, constitutes a hallmark of Alzheimer´s disease (AD) and has been postulated as a critical factor in the disease progression since the identification of several genetic risk factors related to microglial functions. However, the microglial phenotypes in the human pathology have not been determined yet. In this sense, we have previously reported a limited activation and microglial degeneration in the hippocampus of AD patients in contrast to the proinflammatory response long observed in amyloidogenic models. Here, we have further examined the functional/phenotypic profile displayed by microglial cells (activation/degeneration) in two different and vulnerable brain areas of AD patients (frontal cortex and hippocampus). Method Cellular (immunohistochemistry and image analysis) and molecular (qPCR and western blots) approaches have been carried out in samples from non‐demented controls (Braak II) and AD cases (Braak V‐VI). Result Microglial cells from frontal cortex of AD patients showed a generalized and exacerbate activation similar to that observed in APP/PS1 mice. These strongly activated microglial cells, predominantly located surrounding amyloid plaques, could drive the AD pathology and, in consequence, could be implicated in the pathology progression. These findings in the frontal cortex were highly in contrast to the attenuated activation and degenerative morphology showed by microglial cells in the hippocampus of the same AD patients. Conclusion Regional differences in the microglial response exhibit the heterogeneity and complexity of the microglial phenotypes and suggest different functional states of these glial cells in a region‐specific manner. All together, these data need to be considered for better understand the immunological mechanisms underlying AD progression. Modulating brain inflammatory responses might be a promising avenue to prevent cognitive dysfunction in AD patients. 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.