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

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Abstract
Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) 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) A beta deposition in the brain. Next, we identified mechanisms that might cause this effect on AD pathology, more precisely A beta efflux, persistent microglial activation and insufficient A beta clearance, neuronal dysfunction and promotion of A beta 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.
Keywords
Low-grade peripheral inflammation, Brain barriers, Choroid plexus, Blood-CSF barrier, Alzheimer's disease, AMYLOID PRECURSOR PROTEIN, SYSTEMIC INFLAMMATION, CHOROID-PLEXUS, INNATE IMMUNITY, BETA-PEPTIDE, MOUSE MODELS, NEUROINFLAMMATION, MICROGLIA, NEURONS, DYSFUNCTION

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MLA
Xie, Junhua, et al. “Low-Grade Peripheral Inflammation Affects Brain Pathology in the App(NL-G-F)Mouse Model of Alzheimer’s Disease.” ACTA NEUROPATHOLOGICA COMMUNICATIONS, vol. 9, no. 1, 2021, doi:10.1186/s40478-021-01253-z.
APA
Xie, J., Gorlé, N., Vandendriessche, C., Van Imschoot, G., Van Wonterghem, E., Van Cauwenberghe, C., … Vandenbroucke, R. (2021). Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 9(1). https://doi.org/10.1186/s40478-021-01253-z
Chicago author-date
Xie, Junhua, Nina Gorlé, Charysse Vandendriessche, Griet Van Imschoot, Elien Van Wonterghem, Caroline Van Cauwenberghe, Eef Parthoens, et al. 2021. “Low-Grade Peripheral Inflammation Affects Brain Pathology in the App(NL-G-F)Mouse Model of Alzheimer’s Disease.” ACTA NEUROPATHOLOGICA COMMUNICATIONS 9 (1). https://doi.org/10.1186/s40478-021-01253-z.
Chicago author-date (all authors)
Xie, Junhua, Nina Gorlé, Charysse Vandendriessche, Griet Van Imschoot, Elien Van Wonterghem, Caroline Van Cauwenberghe, Eef Parthoens, Evelien Van Hamme, Saskia Lippens, Lien Van Hoecke, and Roosmarijn Vandenbroucke. 2021. “Low-Grade Peripheral Inflammation Affects Brain Pathology in the App(NL-G-F)Mouse Model of Alzheimer’s Disease.” ACTA NEUROPATHOLOGICA COMMUNICATIONS 9 (1). doi:10.1186/s40478-021-01253-z.
Vancouver
1.
Xie J, Gorlé N, Vandendriessche C, Van Imschoot G, Van Wonterghem E, Van Cauwenberghe C, et al. Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease. ACTA NEUROPATHOLOGICA COMMUNICATIONS. 2021;9(1).
IEEE
[1]
J. Xie et al., “Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer’s disease,” ACTA NEUROPATHOLOGICA COMMUNICATIONS, vol. 9, no. 1, 2021.
@article{8727456,
  abstract     = {{Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by the accumulation of amyloid beta (A beta) 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) A beta deposition in the brain. Next, we identified mechanisms that might cause this effect on AD pathology, more precisely A beta efflux, persistent microglial activation and insufficient A beta clearance, neuronal dysfunction and promotion of A beta 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.}},
  articleno    = {{163}},
  author       = {{Xie, Junhua and Gorlé, Nina and Vandendriessche, Charysse and Van Imschoot, Griet and Van Wonterghem, Elien and Van Cauwenberghe, Caroline and Parthoens, Eef and Van Hamme, Evelien and Lippens, Saskia and Van Hoecke, Lien and Vandenbroucke, Roosmarijn}},
  issn         = {{2051-5960}},
  journal      = {{ACTA NEUROPATHOLOGICA COMMUNICATIONS}},
  keywords     = {{Low-grade peripheral inflammation,Brain barriers,Choroid plexus,Blood-CSF barrier,Alzheimer's disease,AMYLOID PRECURSOR PROTEIN,SYSTEMIC INFLAMMATION,CHOROID-PLEXUS,INNATE IMMUNITY,BETA-PEPTIDE,MOUSE MODELS,NEUROINFLAMMATION,MICROGLIA,NEURONS,DYSFUNCTION}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{23}},
  title        = {{Low-grade peripheral inflammation affects brain pathology in the App(NL-G-F)mouse model of Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1186/s40478-021-01253-z}},
  volume       = {{9}},
  year         = {{2021}},
}

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