Age-associated dysregulation of microglial activation is coupled with enhanced BBB permeability and pathology in APP/PS1 mice
Item Type:Journal Article
Citation:Aedín M. Minogue, Raasay S. Jones, Ronan J. Kelly, Claire L. McDonald, Thomas J. Connor and Marina A. Lynch., Age-associated dysregulation of microglial activation is coupled with enhanced BBB permeability and pathology in APP/PS1 mice, Neurobiology of Aging, 2014, 1-30
Minogue et al 2013.pdf (Published (author's copy) - Peer Reviewed) 1.904Mb
Aging adversely affects inflammatory processes in the brain, which has important implications in the context of disease progression. It has been proposed that microglia become dysfunctional with age and may lose their neuroprotective properties leading to chronic neurodegeneration. Here, we sought to characterize inflammatory changes in a mouse model of AD and to delineate differences between normal aging and those associated with disease pathology. A proinflammatory profile, characterized by upregulation of markers of classical activation was evident in APP/PS1 mice, associated with increased interferon (IFN)? concentration and dysregulation of mechanisms designed to limit the proinflammatory response. The data indicate that microglia are not less active with age but alter their phenotype; indeed changes observed in the deactivation state appear to relate to aging rather than disease pathology. We hypothesize that disruption of the BBB, in tandem with an enhanced chemokine profile, permits the infiltration of immune cells serving to reinforce classical activation of microglia through their enhanced responsiveness to IFN?.
Type of material:Journal Article
Series/Report no:Neurobiology of Aging
Availability:Full text available