A regional and cellular analysis of the early intracellular and extracellular accumulation of Aß in the brain of 5XFAD mice.
Neurosci Lett
; 754: 135869, 2021 05 29.
Article
em En
| MEDLINE
| ID: mdl-33857550
ABSTRACT
Intracellular Aß (iAß) expression, extracellular Aß (eAß) plaque formation and microglial reactivity are characteristic neuropathological events of Alzheimer's disease (AD) and have been detected in several transgenic mouse models of this disease. In this work we decided to investigate the early (2-7 months of age) development of these phenomena at both regional and cellular levels in 5XFAD mice, a severe transgenic mouse model of AD. We demonstrated that 1) Aß pathology develops in many but not all brain regions, 2) iAß is transient and almost always followed by eAß in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Aß pathology and in several white matter regions, eAß plaques can appear where no iAß-positive structures were detected. We also showed that male and female mice share a similar regional and cellular pattern of Aß pathology development that is more prominent in females. Early iAß is associated to the activation of microglia, while subsequent formation of eAß plaques is associated with markedly increased density of microglial cells that acquire a characteristic clustered phenotype. Present analysis is relevant to set a reference for pathophysiological studies and to define specific targets for the test of therapeutic interventions in this widely used AD transgenic model.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Córtex Cerebral
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Peptídeos beta-Amiloides
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Placa Amiloide
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Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurosci Lett
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália