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Publication : A regional and cellular analysis of the early intracellular and extracellular accumulation of Aβ in the brain of 5XFAD mice.

First Author  Daini E Year  2021
Journal  Neurosci Lett Volume  754
Pages  135869 PubMed ID  33857550
Mgi Jnum  J:311277 Mgi Id  MGI:6724986
Doi  10.1016/j.neulet.2021.135869 Citation  Daini E, et al. (2021) A regional and cellular analysis of the early intracellular and extracellular accumulation of Abeta in the brain of 5XFAD mice. Neurosci Lett 754:135869
abstractText  Intracellular Abeta (iAbeta) expression, extracellular Abeta (eAbeta) 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) Abeta pathology develops in many but not all brain regions, 2) iAbeta is transient and almost always followed by eAbeta in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Abeta pathology and in several white matter regions, eAbeta plaques can appear where no iAbeta-positive structures were detected. We also showed that male and female mice share a similar regional and cellular pattern of Abeta pathology development that is more prominent in females. Early iAbeta is associated to the activation of microglia, while subsequent formation of eAbeta 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.
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