Liu, Yang, Liu, Xu, Hao, Wenlin, Decker, Yann, Schomburg, Robert, Fueloep, Livia, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Menger, Michael D. and Fassbender, Klaus ORCID: 0000-0003-3596-868X (2014). IKK beta Deficiency in Myeloid Cells Ameliorates Alzheimer's Disease-Related Symptoms and Pathology. J. Neurosci., 34 (39). S. 12982 - 13000. WASHINGTON: SOC NEUROSCIENCE. ISSN 0270-6474

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Abstract

Alzheimer's disease (AD) is characterized by extracellular amyloid-beta (A beta) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and A beta clearance. However, studies examining innate immunity in A beta pathology and neuronal degeneration have produced conflicting results. In this study, we investigated the pathogenic role of innate immunity in AD by ablating a key signaling molecule, IKK beta, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKK beta in myeloid cells, especially microglia, simultaneously reduced inflammatory activation andA beta load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKK beta deficiency enhanced microglial recruitment to A beta deposits and facilitated A beta internalization, perhaps by inhibiting TGF-beta-SMAD2/3 signaling, but did not affect A beta production and efflux. Therefore, inhibition of IKK beta signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing A beta clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Liu, YangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, XuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hao, WenlinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Decker, YannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schomburg, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fueloep, LiviaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Menger, Michael D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fassbender, KlausUNSPECIFIEDorcid.org/0000-0003-3596-868XUNSPECIFIED
URN: urn:nbn:de:hbz:38-428470
DOI: 10.1523/JNEUROSCI.1348-14.2014
Journal or Publication Title: J. Neurosci.
Volume: 34
Number: 39
Page Range: S. 12982 - 13000
Date: 2014
Publisher: SOC NEUROSCIENCE
Place of Publication: WASHINGTON
ISSN: 0270-6474
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BLOOD-BRAIN-BARRIER; CEREBRAL AMYLOID ANGIOPATHY; NF-KAPPA-B; MOUSE MODEL; MICROGLIAL ACTIVATION; TRANSGENIC MICE; ALTERNATIVE ACTIVATION; MONONUCLEAR PHAGOCYTES; COGNITIVE DEFICITS; PRECURSOR PROTEINMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/42847

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