Ablation of reactive astrocytes exacerbates disease pathology in a model of Alzheimer's disease. Issue 5 (4th December 2019)

• Record Type: Journal Article
• Authors: Katsouri, Loukia; Birch, Amy M.; Renziehausen, Alexander W. J.; Zach, Carolin; Aman, Yahyah; Steeds, Hannah; Bonsu, Angela; Palmer, Emily O. C.; Mirzaei, Nazanin; Ries, Miriam; Sastre, Magdalena
• Is Part Of: Glia. Volume 68:Issue 5(2020)
• Page Start: 1017
• Page End: 1030
• Publication Date: 2019-12-04
• Subjects: astrocyte -- Aβ -- glial fibrillary acidic protein (GFAP) -- inflammation -- synapses; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23759
• Languages: English
• ISSNs: 0894-1491

Abstract

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. Main points: Depletion of proliferating astrocytes in APP23 mice leads to reduced amyloid degradation. Loss of proliferating astrocytes results in increased memory deficits associated with synaptic and neuronal loss. Ablation of proliferating astrocytes increases the expression of pro‐inflammatory cytokines.