Open AccessCounteracting the effects of TNF receptor‐1 has therapeutic potential in Alzheimer's disease
Author(s) -
Steeland Sophie,
Gorlé Nina,
Vandendriessche Charysse,
Balusu Sriram,
Brkic Marjana,
Van Cauwenberghe Caroline,
Van Imschoot Griet,
Van Wonterghem Elien,
De Rycke Riet,
Kremer Anneke,
Lippens Saskia,
Stopa Edward,
Johanson Conrad E,
Libert Claude,
Vandenbroucke Roosmarijn E
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708300
Subject(s) - choroid plexus , neuroinflammation , tumor necrosis factor alpha , pathogenesis , inflammation , blood–brain barrier , medicine , receptor , immunology , pharmacology , endocrinology , central nervous system
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. TNFR 1, 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 / PS 1 mice and intracerebroventricular (icv) AβO injection. TNFR 1 contributes to the morphological damage of CPE cells in AD , and TNFR 1 abrogation reduces brain inflammation and prevents blood– CSF barrier impairment. In APP / PS 1 transgenic mice, TNFR 1 deficiency ameliorated amyloidosis. Ultimately, genetic and pharmacological blockage of TNFR 1 rescued from the induced cognitive impairments. Our data indicate that TNFR 1 is a promising therapeutic target for AD treatment.