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Open Access 01-12-2021 | Alzheimer's Disease | Research

Low-grade peripheral inflammation affects brain pathology in the App^NL-G-Fmouse model of Alzheimer’s disease

Authors: Junhua Xie, Nina Gorlé, Charysse Vandendriessche, Griet Van Imschoot, Elien Van Wonterghem, Caroline Van Cauwenberghe, Eef Parthoens, Evelien Van Hamme, Saskia Lippens, Lien Van Hoecke, Roosmarijn E. Vandenbroucke

Published in: Acta Neuropathologica Communications | Issue 1/2021

Abstract

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.

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Title: Low-grade peripheral inflammation affects brain pathology in the AppNL-G-Fmouse model of Alzheimer’s disease
Authors: Junhua Xie
Nina Gorlé
Charysse Vandendriessche
Griet Van Imschoot
Elien Van Wonterghem
Caroline Van Cauwenberghe
Eef Parthoens
Evelien Van Hamme
Saskia Lippens
Lien Van Hoecke
Roosmarijn E. Vandenbroucke
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Alzheimer's Disease
Alzheimer's Disease
Pathology
Published in: Acta Neuropathologica Communications / Issue 1/2021
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/s40478-021-01253-z

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Low-grade peripheral inflammation affects brain pathology in the App^NL-G-Fmouse model of Alzheimer’s disease

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