Low-grade peripheral inflammation affects brain pathology in the App NL-G-F mouse model of Alzheimer's disease.

Autor: Xie J; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Gorlé N; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Vandendriessche C; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Van Imschoot G; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Van Wonterghem E; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Van Cauwenberghe C; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Parthoens E; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium.; VIB BioImaging Core, VIB, Ghent, Belgium., Van Hamme E; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; VIB BioImaging Core, VIB, Ghent, Belgium., Lippens S; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; VIB BioImaging Core, VIB, Ghent, Belgium., Van Hoecke L; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium., Vandenbroucke RE; VIB-UGent Center for Inflammation Research, Technologiepark-Zwijnaarde 71, 9052, Ghent, Belgium. Roosmarijn.Vandenbroucke@irc.VIB-UGent.be.; Department of Biomedical Molecular Biology, Ghent University, 9000, Ghent, Belgium. Roosmarijn.Vandenbroucke@irc.VIB-UGent.be.
Jazyk: angličtina
Zdroj: Acta neuropathologica communications [Acta Neuropathol Commun] 2021 Oct 07; Vol. 9 (1), pp. 163. Date of Electronic Publication: 2021 Oct 07.
DOI: 10.1186/s40478-021-01253-z
Abstrakt: Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid β (Aβ) and neurofibrillary tangles. The last decade, it became increasingly clear that neuroinflammation plays a key role in both the initiation and progression of AD. Moreover, also the presence of peripheral inflammation has been extensively documented. However, it is still ambiguous whether this observed inflammation is cause or consequence of AD pathogenesis. Recently, this has been studied using amyloid precursor protein (APP) overexpression mouse models of AD. However, the findings might be confounded by APP-overexpression artifacts. Here, we investigated the effect of low-grade peripheral inflammation in the APP knock-in (App NL-G-F ) mouse model. This revealed that low-grade peripheral inflammation affects (1) microglia characteristics, (2) blood-cerebrospinal fluid barrier integrity, (3) peripheral immune cell infiltration and (4) Aβ deposition in the brain. Next, we identified mechanisms that might cause this effect on AD pathology, more precisely Aβ efflux, persistent microglial activation and insufficient Aβ clearance, neuronal dysfunction and promotion of Aβ aggregation. Our results further strengthen the believe that even low-grade peripheral inflammation has detrimental effects on AD progression and may further reinforce the idea to modulate peripheral inflammation as a therapeutic strategy for AD.
(© 2021. The Author(s).)
Databáze: MEDLINE
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