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Sci Rep. 2017 Dec 19;7(1):17762. doi: 10.1038/s41598-017-17999-3.

Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation.

Author information

1
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
2
Department of Neurology, University of California, San Francisco, San Francisco, CA, 94158, USA.
3
Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan.
4
Department of Neurosurgery, Japan Community Health Care Organization Kyushu Hospital, Kitakyushu, 806-8501, Japan.
5
Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
6
Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
7
Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
8
Hisayama Research Institute for Lifestyle Diseases, Hisayama, Fukuoka, Japan.
9
Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697, USA.
10
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. yusaku@bioreg.kyushu-u.c.jp.

Abstract

Alzheimer's disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofibrillary tangles. Oxidative stress and inflammation are considered to play an important role in the development and progression of AD. However, the extent to which these events contribute to the Aβ pathologies remains unclear. We performed inter-species comparative gene expression profiling between AD patient brains and the App NL-G-F/NL-G-F and 3xTg-AD-H mouse models. Genes commonly altered in App NL-G-F/NL-G-F and human AD cortices correlated with the inflammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfbr2, and Vim) was increased in the App NL-G-F/NL-G-F cortex as Aβ amyloidosis progressed with exacerbated gliosis, while genes commonly altered in the 3xTg-AD-H and human AD cortices correlated with neurological disease. The App NL-G-F/NL-G-F cortex also had altered expression of genes (Abi3, Apoe, Bin2, Cd33, Ctsc, Dock2, Fcer1g, Frmd6, Hck, Inpp5D, Ly86, Plcg2, Trem2, Tyrobp) defined as risk factors for AD by genome-wide association study or identified as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinflammatory response and provide a better understanding of the involvement of gender effects in the development of AD.

PMID:
29259249
PMCID:
PMC5736730
DOI:
10.1038/s41598-017-17999-3
[Indexed for MEDLINE]
Free PMC Article

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