Journal
ALZHEIMERS & DEMENTIA
Volume 14, Issue 2, Pages 215-229Publisher
WILEY
DOI: 10.1016/j.jalz.2017.08.012
Keywords
Alzheimer's disease; Differential expression; Convergent functional genomic; Upstream regulator; Database
Categories
Funding
- Key Program of National Natural Science Foundation of China (NSFC) [31730037]
- Bureau of Frontier Sciences and Education [QYZDJ-SSW-SMC005]
- West Light Foundation of the Chinese Academy of Sciences
- French National Foundation on Alzheimer's disease and related disorders
- LABEX (laboratory of excellence program investment for the future) DISTALZ grant
- Inserm
- Institut Pasteur de Lille
- Universite de Lille 2
- Lille University Hospital
- Medical Research Council [503480]
- Alzheimer's Research UK [503176]
- Wellcome Trust [082604/2/07/Z]
- German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) [01GI0102, 01GI0711, 01GI0420]
- NIH/NIA [R01 AG033193, U01 AG032984, U24 AG021886, U01 AG016976, ADGC-10-196728]
- NIA [AG081220]
- AGES [N01-AG-12100]
- NHLBI [R01 HL105756]
- Icelandic Heart Association
- Erasmus Medical Center
- Erasmus University
- [XDB02020003]
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Introduction: Profiling the spatial-temporal expression pattern and characterizing the regulatory networks of brain tissues are vital for understanding the pathophysiology of Alzheimer's disease (AD). Methods: We performed a systematic integrated analysis of expression profiles of AD-affected brain tissues (684 AD and 562 controls). A network-based convergent functional genomic approach was used to prioritize possible regulator genes during AD development, followed by functional characterization. Results: We generated a complete list of differentially expressed genes and hub genes of the transcriptomic network in AD brain and constructed a Web server (www.alzdata.org) for public access. Seventeen hub genes active at the early stages, especially YAP1, were recognized as upstream regulators of the AD network. Cellular assays proved that early alteration of YAP1 could promote AD by influencing the whole transcriptional network. Discussion: Early expression disturbance of hub genes is an important feature of AD development, and interfering with this process may reverse the disease progression. (C) 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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