PT  - JOURNAL ARTICLE
AU  - Yang Liu
AU  - Xu Liu
AU  - Wenlin Hao
AU  - Yann Decker
AU  - Robert Schomburg
AU  - Livia Fülöp
AU  - Manolis Pasparakis
AU  - Michael D. Menger
AU  - Klaus Fassbender
TI  - IKKβ Deficiency in Myeloid Cells Ameliorates Alzheimer's Disease-Related Symptoms and Pathology
AID  - 10.1523/JNEUROSCI.1348-14.2014
DP  - 2014 Sep 24
TA  - The Journal of Neuroscience
PG  - 12982--12999
VI  - 34
IP  - 39
4099  - http://www.jneurosci.org/content/34/39/12982.short
4100  - http://www.jneurosci.org/content/34/39/12982.full
SO  - J. Neurosci.2014 Sep 24; 34
AB  - Alzheimer's disease (AD) is characterized by extracellular amyloid-β (Aβ) deposits and microglia-dominated inflammatory activation. Innate immune signaling controls microglial inflammatory activities and Aβ clearance. However, studies examining innate immunity in Aβ 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, IKKβ, specifically in the myeloid cells of TgCRND8 APP-transgenic mice. Deficiency of IKKβ in myeloid cells, especially microglia, simultaneously reduced inflammatory activation and Aβ load in the brain and these effects were associated with reduction of cognitive deficits and preservation of synaptic structure proteins. IKKβ deficiency enhanced microglial recruitment to Aβ deposits and facilitated Aβ internalization, perhaps by inhibiting TGF-β-SMAD2/3 signaling, but did not affect Aβ production and efflux. Therefore, inhibition of IKKβ signaling in myeloid cells improves cognitive functions in AD mice by reducing inflammatory activation and enhancing Aβ clearance. These results contribute to a better understanding of AD pathogenesis and could offer a new therapeutic option for delaying AD progression.