Katsouri, L;
Birch, AM;
Renziehausen, AWJ;
Zach, C;
Aman, Y;
Steeds, H;
Bonsu, A;
... Sastre, M; + view all
(2019)
Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease.
GLIA
, 68
(5)
pp. 1017-1030.
10.1002/glia.23759.
Preview |
Text
Katsouri_et_al-2019-Glia.pdf - Published Version Download (6MB) | Preview |
Abstract
The role of astrocytes in the progression of Alzheimer's disease (AD) remains poorly understood. We assessed the consequences of ablating astrocytic proliferation in 9 months old double transgenic APP23/GFAP-TK mice. Treatment of these mice with the antiviral agent ganciclovir conditionally ablates proliferating reactive astrocytes. The loss of proliferating astrocytes resulted in significantly increased levels of monomeric amyloid-β (Aβ) in brain homogenates, associated with reduced enzymatic degradation and clearance mechanisms. In addition, our data revealed exacerbated memory deficits in mice lacking proliferating astrocytes concomitant with decreased levels of synaptic markers and higher expression of pro-inflammatory cytokines. Our data suggest that loss of reactive astrocytes in AD aggravates amyloid pathology and memory loss, possibly via disruption of amyloid clearance and enhanced neuroinflammation.
| Type: | Article |
|---|---|
| Title: | Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/glia.23759 |
| Publisher version: | https://doi.org/10.1002/glia.23759 |
| Language: | English |
| Additional information: | This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Keywords: | astrocyte, Aβ, glial fibrillary acidic protein (GFAP), inflammation, synapses |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > The Sainsbury Wellcome Centre |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10087814 |
Archive Staff Only
 |
View Item |
