Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Liu, Yang UNSPECIFIED UNSPECIFIED UNSPECIFIED Liu, Xu UNSPECIFIED UNSPECIFIED UNSPECIFIED Hao, Wenlin UNSPECIFIED UNSPECIFIED UNSPECIFIED Decker, Yann UNSPECIFIED UNSPECIFIED UNSPECIFIED Schomburg, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Fueloep, Livia UNSPECIFIED UNSPECIFIED UNSPECIFIED Pasparakis, Manolis UNSPECIFIED orcid.org/0000-0002-9870-0966 UNSPECIFIED Menger, Michael D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fassbender, Klaus UNSPECIFIED orcid.org/0000-0003-3596-868X UNSPECIFIED
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:	Keywords Language BLOOD-BRAIN-BARRIER; CEREBRAL AMYLOID ANGIOPATHY; NF-KAPPA-B; MOUSE MODEL; MICROGLIAL ACTIVATION; TRANSGENIC MICE; ALTERNATIVE ACTIVATION; MONONUCLEAR PHAGOCYTES; COGNITIVE DEFICITS; PRECURSOR PROTEIN Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42847