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

Erika Castillo, Julio Leon, Guianfranco Mazzei, Nona Abolhassani, Naoki Haruyama, Takashi Saito, Takaomi Saido, Masaaki Hokama, Toru Iwaki, Tomoyuki Ohara, Toshiharu Ninomiya, Yutaka Kiyohara, Kunihiko Sakumi, Frank M. Laferla, Yusaku Nakabeppu

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Article number17762
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017

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Gene Expression Profiling
Amyloidosis
Alzheimer Disease
Genes
Neurofibrillary Tangles
Gliosis
Genome-Wide Association Study
Immune System Diseases
Apolipoproteins E
Amyloid
Dementia
Oxidative Stress
Pathology
Inflammation
Gene Expression

All Science Journal Classification (ASJC) codes

  • General

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Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation. / Castillo, Erika; Leon, Julio; Mazzei, Guianfranco; Abolhassani, Nona; Haruyama, Naoki; Saito, Takashi; Saido, Takaomi; Hokama, Masaaki; Iwaki, Toru; Ohara, Tomoyuki; Ninomiya, Toshiharu; Kiyohara, Yutaka; Sakumi, Kunihiko; Laferla, Frank M.; Nakabeppu, Yusaku.

In: Scientific reports, Vol. 7, No. 1, 17762, 01.12.2017.

Research output: Contribution to journalArticle

Castillo, Erika ; Leon, Julio ; Mazzei, Guianfranco ; Abolhassani, Nona ; Haruyama, Naoki ; Saito, Takashi ; Saido, Takaomi ; Hokama, Masaaki ; Iwaki, Toru ; Ohara, Tomoyuki ; Ninomiya, Toshiharu ; Kiyohara, Yutaka ; Sakumi, Kunihiko ; Laferla, Frank M. ; Nakabeppu, Yusaku. / Comparative profiling of cortical gene expression in Alzheimer's disease patients and mouse models demonstrates a link between amyloidosis and neuroinflammation. In: Scientific reports. 2017 ; Vol. 7, No. 1.
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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.",
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AU - Castillo, Erika

AU - Leon, Julio

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AU - Abolhassani, Nona

AU - Haruyama, Naoki

AU - Saito, Takashi

AU - Saido, Takaomi

AU - Hokama, Masaaki

AU - Iwaki, Toru

AU - Ohara, Tomoyuki

AU - Ninomiya, Toshiharu

AU - Kiyohara, Yutaka

AU - Sakumi, Kunihiko

AU - Laferla, Frank M.

AU - Nakabeppu, Yusaku

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