A regional and cellular analysis of the early intracellular and extracellular accumulation of Aβ in the brain of 5XFAD mice. (29th May 2021)

• Record Type: Journal Article
• Authors: Daini, Eleonora; Secco, Valentina; Liao, Wenjie; Zoli, Michele; Vilella, Antonietta
• Is Part Of: Neuroscience letters. Volume 754(2021)
• Publication Date: 2021-05-29
• Subjects: Intracellular Aβ accumulation -- Amyloid plaque deposition -- 5XFAD mice -- Microglial reactivity -- Alzheimer's disease; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2021.135869
• Languages: English
• ISSNs: 0304-3940

Abstract

Graphical abstract: Highlights: Aβ accumulation and deposition occur in many but not all brain regions. Intracellular Aβ expression is transient and almost always followed by extracellular Aβplaque formation. Aβ plaque formation is not necessarily preceded by local intracellular Aβ expression. Abstract: Intracellular Aβ (iAβ) expression, extracellular Aβ (eAβ) 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) Aβ pathology develops in many but not all brain regions, 2) iAβ is transient and almost always followed by eAβ in grey matter regions, and the respective levels are roughly proportional, and 3) in about 1/3 of the grey matter regions with Aβ pathology and in several white matter regions, eAβ plaques can appear where no iAβ-positive structures were detected. We also showed that male and female mice share a similar regional and cellular pattern of Aβ pathology development that is more prominent in females. Early iAβ is associated to the activation of microglia, while subsequent formation of eAβ 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.