1 SCIENTIFIC REPORTS | (2017) 7:17762 | DOI:10.1038/s41598-017-17999-3 www.nature.com/scientificreports Comparative profling of cortical gene expression in Alzheimer’s disease patients and mouse models demonstrates a link between amyloidosis and neuroinfammation Erika Castillo 1 , Julio Leon 1,8 , Guianfranco Mazzei 1 , Nona Abolhassani 1 , Naoki Haruyama 1 , Takashi Saito 2 , Takaomi Saido 2 , Masaaki Hokama 1,9 , Toru Iwaki 3 , Tomoyuki Ohara 4 , Toshiharu Ninomiya 5 , Yutaka Kiyohara 6 , Kunihiko Sakumi 1 , Frank M. LaFerla 7 & Yusaku Nakabeppu 1 Alzheimer’s disease (AD) is the most common form of dementia, characterized by accumulation of amyloid β (Aβ) and neurofbrillary tangles. Oxidative stress and infammation 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 profling 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 infammatory response or immunological disease. Among them, expression of AD-related genes (C4a/C4b, Cd74, Ctss, Gfap, Nfe2l2, Phyhd1, S100b, Tf, Tgfr2, 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) defned as risk factors for AD by genome-wide association study or identifed as genetic nodes in late-onset AD. These results suggest a strong correlation between cortical Aβ amyloidosis and the neuroinfammatory response and provide a better understanding of the involvement of gender efects in the development of AD. Dementia afects over 47 million people throughout the world, and this number is likely to increase to more than 131 million by 2050 1 . Alzheimer’s disease (AD) is the most common form of dementia, and amyloid β (Aβ) 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 Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Saitama, Japan. 3 Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812–8582, Japan. 4 Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812–8582, Japan. 5 Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812–8582, Japan. 6 Hisayama Research Institute for Lifestyle Diseases, Hisayama, Fukuoka, Japan. 7 Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697, USA. 8 Present address: Department of Neurology, University of California, San Francisco, San Francisco, CA, 94158, USA. 9 Present address: Department of Neurosurgery, Japan Community Health Care Organization Kyushu Hospital, Kitakyushu, 806–8501, Japan. Correspondence and requests for materials should be addressed to Y.N. (email: yusaku@bioreg.kyushu-u.c.jp) Received: 13 January 2017 Accepted: 5 December 2017 Published: xx xx xxxx OPEN There are amendments to this paper