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Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer’s disease

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Title: Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer’s disease
Authors: Katsouri, L
Birch, A
Renziehausen, A
Zach, C
Aman, Y
Steeds, H
Bonsu, A
Palmer, E
Mirzaei, N
Ries, M
Sastre, M
Item Type: Journal Article
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.
Issue Date: May-2020
Date of Acceptance: 21-Nov-2019
URI: http://hdl.handle.net/10044/1/75381
DOI: 10.1002/glia.23759
ISSN: 0894-1491
Publisher: Wiley
Start Page: 1017
End Page: 1030
Journal / Book Title: Glia
Volume: 68
Issue: 5
Copyright Statement: © 2019 The Authors. Glia published by Wiley Periodicals, Inc. 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.
Sponsor/Funder: Alzheimer's Research UK (ARUK)
Alzheimer's Research UK (ARUK)
Alzheimer's Research UK (ARUK)
Funder's Grant Number: ART/PPG2009B/10
ART-PG2011-12
P52427
Keywords: Science & Technology
Life Sciences & Biomedicine
Neurosciences
Neurosciences & Neurology
astrocyte
A beta
glial fibrillary acidic protein (GFAP)
inflammation
synapses
A-BETA METABOLISM
MOUSE MODELS
SECRETED PROTEINS
GLIA
PROLIFERATION
EXPRESSION
MICE
DEGRADATION
MECHANISMS
CLEARANCE

astrocyte
glial fibrillary acidic protein (GFAP)
inflammation
synapses
Neurology & Neurosurgery
1109 Neurosciences
Publication Status: Published online
Online Publication Date: 2019-12-04
Appears in Collections:Department of Brain Sciences