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Title: The role of pro-inflammatory S100A9 in Alzheimer’s disease amyloid-neuroinflammatory cascade
Authors: Zhao, Lina
Jia, Xueen
Shankar, S K
Olofsson, Anders
Brännström, Thomas
Mu, Yuguang
Gräslund, Astrid
Morozova-Roche, Ludmilla A
Jarvet, Jüri
Wang, Chao
Klechikov, Alexey G
Gharibyan, Anna L
Wärmländer, Sebastian K T S
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2013
Source: Wang, C., Klechikov, A. G., Gharibyan, A. L., Wärmländer, S. K. T. S., Jarvet, J., Zhao, L., et al. (2014). The role of pro-inflammatory S100A9 in Alzheimer’s disease amyloid-neuroinflammatory cascade. Acta Neuropathologica, 127(4), 507-522.
Series/Report no.: Acta neuropathologica
Abstract: Pro-inflammatory S100A9 protein is increasingly recognized as an important contributor to inflammation-related neurodegeneration. Here, we provide insights into S100A9 specific mechanisms of action in Alzheimer’s disease (AD). Due to its inherent amyloidogenicity S100A9 contributes to amyloid plaque formation together with Aβ. In traumatic brain injury (TBI) S100A9 itself rapidly forms amyloid plaques, which were reactive with oligomer-specific antibodies, but not with Aβ and amyloid fibrillar antibodies. They may serve as precursor-plaques for AD, implicating TBI as an AD risk factor. S100A9 was observed in some hippocampal and cortical neurons in TBI, AD and non-demented aging. In vitro S100A9 forms neurotoxic linear and annular amyloids resembling Aβ protofilaments. S100A9 amyloid cytotoxicity and native S100A9 pro-inflammatory signaling can be mitigated by its co-aggregation with Aβ, which results in a variety of micron-scale amyloid complexes. NMR and molecular docking demonstrated transient interactions between native S100A9 and Aβ. Thus, abundantly present in AD brain pro-inflammatory S100A9, possessing also intrinsic amyloidogenic properties and ability to modulate Aβ aggregation, can serve as a link between the AD amyloid and neuroinflammatory cascades and as a prospective therapeutic target.
ISSN: 0001-6322
DOI: 10.1007/s00401-013-1208-4
Schools: School of Biological Sciences 
Rights: © 2013 The Author(s). This paper was published in Acta Neuropathologica and is made available as an electronic reprint (preprint) with permission of the Author(s). The paper can be found at the following official DOI:  One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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