Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease
Article first published online: 18 MAR 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 4, pages 584–595, August 2014
How to Cite
Baron, R., Babcock, A. A., Nemirovsky, A., Finsen, B. and Monsonego, A. (2014), Accelerated microglial pathology is associated with Aβ plaques in mouse models of Alzheimer's disease. Aging Cell, 13: 584–595. doi: 10.1111/acel.12210
- Issue published online: 29 JUL 2014
- Article first published online: 18 MAR 2014
- Manuscript Accepted: 12 JAN 2014
- Israel Science Foundation
- Danish Medical Research Council
- Lundbeck Foundation
- The Danish Alzheimer Research Foundation
- Alzheimer's disease;
- amyloid beta-peptide;
Microglia integrate within the neural tissue with a distinct ramified morphology through which they scan the surrounding neuronal network. Here, we used a digital tool for the quantitative morphometric characterization of fine cortical microglial structures in mice, and the changes they undergo with aging and in Alzheimer's-like disease. We show that, compared with microglia in young mice, microglia in old mice are less ramified and possess fewer branches and fine processes along with a slightly increased proinflammatory cytokine expression. A similar microglial pathology appeared 6–12 months earlier in mouse models of Alzheimer's disease (AD), along with a significant increase in brain parenchyma lacking coverage by microglial processes. We further demonstrate that microglia near amyloid plaques acquire unique activated phenotypes with impaired process complexity. We thus show that along with a chronic proinflammatory reaction in the brain, aging causes a significant reduction in the capacity of microglia to scan their environment. This type of pathology is markedly accelerated in mouse models of AD, resulting in a severe microglial process deficiency, and possibly contributing to enhanced cognitive decline.