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

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 pres...

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Autores principales: Xie, Junhua, Gorlé, Nina, Vandendriessche, Charysse, Van Imschoot, Griet, Van Wonterghem, Elien, Van Cauwenberghe, Caroline, Parthoens, Eef, Van Hamme, Evelien, Lippens, Saskia, Van Hoecke, Lien, Vandenbroucke, Roosmarijn E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499584/
https://www.ncbi.nlm.nih.gov/pubmed/34620254
http://dx.doi.org/10.1186/s40478-021-01253-z
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author Xie, Junhua
Gorlé, Nina
Vandendriessche, Charysse
Van Imschoot, Griet
Van Wonterghem, Elien
Van Cauwenberghe, Caroline
Parthoens, Eef
Van Hamme, Evelien
Lippens, Saskia
Van Hoecke, Lien
Vandenbroucke, Roosmarijn E.
author_facet Xie, Junhua
Gorlé, Nina
Vandendriessche, Charysse
Van Imschoot, Griet
Van Wonterghem, Elien
Van Cauwenberghe, Caroline
Parthoens, Eef
Van Hamme, Evelien
Lippens, Saskia
Van Hoecke, Lien
Vandenbroucke, Roosmarijn E.
author_sort Xie, Junhua
collection PubMed
description 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. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-021-01253-z.
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spelling pubmed-84995842021-10-08 Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease Xie, Junhua Gorlé, Nina Vandendriessche, Charysse Van Imschoot, Griet Van Wonterghem, Elien Van Cauwenberghe, Caroline Parthoens, Eef Van Hamme, Evelien Lippens, Saskia Van Hoecke, Lien Vandenbroucke, Roosmarijn E. Acta Neuropathol Commun Research 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. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-021-01253-z. BioMed Central 2021-10-07 /pmc/articles/PMC8499584/ /pubmed/34620254 http://dx.doi.org/10.1186/s40478-021-01253-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Xie, Junhua
Gorlé, Nina
Vandendriessche, Charysse
Van Imschoot, Griet
Van Wonterghem, Elien
Van Cauwenberghe, Caroline
Parthoens, Eef
Van Hamme, Evelien
Lippens, Saskia
Van Hoecke, Lien
Vandenbroucke, Roosmarijn E.
Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease
title Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease
title_full Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease
title_fullStr Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease
title_full_unstemmed Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease
title_short Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease
title_sort low-grade peripheral inflammation affects brain pathology in the app(nl-g-f)mouse model of alzheimer’s disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499584/
https://www.ncbi.nlm.nih.gov/pubmed/34620254
http://dx.doi.org/10.1186/s40478-021-01253-z
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