Title
Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation
Date Issued
01 December 2017
Access level
open access
Resource Type
journal article
Author(s)
Castillo E.
Abolhassani N.
Haruyama N.
Saito T.
Saido T.
Hokama M.
Iwaki T.
Ohara T.
Ninomiya T.
Kiyohara Y.
Sakumi K.
Laferla F.M.
Nakabeppu Y.
Medical Institute of Bioregulation
Medical Institute of Bioregulation
Publisher(s)
Nature Publishing Group
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.
Volume
7
Issue
1
Number
17762
Language
English
OCDE Knowledge area
Neurología clínica
Psiquiatría
Scopus EID
2-s2.0-85038634372
PubMed ID
Source
Scientific Reports
ISSN of the container
20452322
Sponsor(s)
This work was partly supported by grants from the Ministry of Health, Labour and Welfare, Japan (grant number H20-ninchisho-ippan-004 to Y.N.), the Research and Development Grants for Dementia from the Japan Agency for Medical Research and Development (H25-ninchisho-ippann-004 to Y.N.), and the Japan Society for the Promotion of Science (grant numbers 22221004, 15K15085, 17H01391 to Y.N.). We thank Y. Ohyagi (Faculty of Medical Sciences, Kyushu University) for transferring the 3xTg-AD-H mice; and E. Koba and M. Oda (Laboratory for Technical Supports Medical Institute of Bioregulation, Kyushu University) for performing the microarray hybridisation, scanning and image analysis. We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript. We also thank S. Kitamura, K. Nakabeppu, and T. Kuwano for their technical assistance.
Sources of information:
Directorio de Producción Científica
Scopus