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Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease

Sophie Steeland (UGent) , Nina Gorlé (UGent) , Charysse Vandendriessche (UGent) , Sriram Balusu (UGent) , Marjana Brkić (UGent) , Caroline Van Cauwenberghe (UGent) , Griet Van Imschoot (UGent) , Elien Van Wonterghem (UGent) , Riet De Rycke (UGent) , Anna Kremer (UGent) , et al.
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Abstract
Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death. The blood-cerebrospinal fluid (CSF) barrier consists of a monolayer of choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE cell morphology. Here, we report that TNF is the main inflammatory upstream mediator in choroid plexus tissue in AD patients. This was confirmed in two murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv) AO injection. TNFR1 contributes to the morphological damage of CPE cells in AD, and TNFR1 abrogation reduces brain inflammation and prevents blood-CSF barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued from the induced cognitive impairments. Our data indicate that TNFR1 is a promising therapeutic target for AD treatment.
Keywords
NECROSIS-FACTOR-ALPHA, AMYLOID-BETA OLIGOMERS, KAPPA-B PATHWAY, CHOROID-PLEXUS, TRANSGENIC MICE, BLOOD-BRAIN, GLUTAMATE RELEASE, GENETIC, DELETION, MEMORY DEFICITS, GLIAL RESPONSE, Alzheimer's disease, blood-CSF barrier, choroid plexus, therapy, TNF, receptor 1

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Citation

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Chicago
Steeland, Sophie, Nina Gorlé, Charysse Vandendriessche, Sriram Balusu, Marjana Brkić, Caroline Van Cauwenberghe, Griet Van Imschoot, et al. 2018. “Counteracting the Effects of TNF Receptor-1 Has Therapeutic Potential in Alzheimer’s Disease.” Embo Molecular Medicine 10 (4).
APA
Steeland, S., Gorlé, N., Vandendriessche, C., Balusu, S., Brkić, M., Van Cauwenberghe, C., Van Imschoot, G., et al. (2018). Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer’s disease. EMBO MOLECULAR MEDICINE, 10(4).
Vancouver
1.
Steeland S, Gorlé N, Vandendriessche C, Balusu S, Brkić M, Van Cauwenberghe C, et al. Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer’s disease. EMBO MOLECULAR MEDICINE. 2018;10(4).
MLA
Steeland, Sophie, Nina Gorlé, Charysse Vandendriessche, et al. “Counteracting the Effects of TNF Receptor-1 Has Therapeutic Potential in Alzheimer’s Disease.” EMBO MOLECULAR MEDICINE 10.4 (2018): n. pag. Print.
@article{8561168,
  abstract     = {Alzheimer's disease (AD) is the most common form of dementia, and neuroinflammation is an important hallmark of the pathogenesis. Tumor necrosis factor (TNF) might be detrimental in AD, though the results coming from clinical trials on anti-TNF inhibitors are inconclusive. TNFR1, one of the TNF signaling receptors, contributes to the pathogenesis of AD by mediating neuronal cell death. The blood-cerebrospinal fluid (CSF) barrier consists of a monolayer of choroid plexus epithelial (CPE) cells, and AD is associated with changes in CPE cell morphology. Here, we report that TNF is the main inflammatory upstream mediator in choroid plexus tissue in AD patients. This was confirmed in two murine AD models: transgenic APP/PS1 mice and intracerebroventricular (icv) AO injection. TNFR1 contributes to the morphological damage of CPE cells in AD, and TNFR1 abrogation reduces brain inflammation and prevents blood-CSF barrier impairment. In APP/PS1 transgenic mice, TNFR1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR1 rescued from the induced cognitive impairments. Our data indicate that TNFR1 is a promising therapeutic target for AD treatment.},
  articleno    = {e8300},
  author       = {Steeland, Sophie and Gorl{\'e}, Nina and Vandendriessche, Charysse and Balusu, Sriram and Brki\'{c}, Marjana and Van Cauwenberghe, Caroline and Van Imschoot, Griet and Van Wonterghem, Elien and De Rycke, Riet and Kremer, Anna and Lippens, Saskia and Stopa, Edward and Johanson, Conrad E and Libert, Claude and Vandenbroucke, Roosmarijn},
  issn         = {1757-4676},
  journal      = {EMBO MOLECULAR MEDICINE},
  language     = {eng},
  number       = {4},
  pages        = {22},
  title        = {Counteracting the effects of TNF receptor-1 has therapeutic potential in Alzheimer's disease},
  url          = {http://dx.doi.org/10.15252/emmm.201708300},
  volume       = {10},
  year         = {2018},
}

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