Affiliations: [a] CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China | [b] University of Chinese Academy of Sciences, Beijing, China | [c] Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Australia | [d] UC Davis Genome Center and Department of Biomedical Engineering, Davis, CA, USA | [e] Center of Alzheimer's disease, Beijing Institute for Brain Disorders, Beijing, China
Correspondence:
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Correspondence to: Hongxing Lei, Beijing Institute of Genomics, Beijing, China. Tel.: +1 086 10 84097276; E-mail: leihx@big.ac.cn; Yong Duan, UC Davis Genome Center, Davis, CA, USA. Tel.: +530 754 7632; E-mail: duan@ucdavis.edu.
Note: [1] These authors contributed equally to this work.
Abstract: The brain transcriptome of Alzheimer's disease (AD) reflects the prevailing disease mechanism at the gene expression level. However, thousands of genes have been reported to be dysregulated in AD brains in existing studies, and the consistency or discrepancy among these studies has not been thoroughly examined. Toward this end, we conducted a comprehensive survey of the brain transcriptome datasets for AD and other neurological diseases. We first demonstrated that the frequency of observed dysregulation in AD was highly correlated with the reproducibility of the dysregulation. Based on this observation, we selected 100 genes with the highest frequency of dysregulation to illustrate the core perturbation in AD brains. The dysregulation of these genes was validated in several independent datasets for AD. We further identified 12 genes with strong correlation of gene expression with disease progression. The relevance of these genes to disease progression was also validated in an independent dataset. Interestingly, we found a transcriptional “cushion” for these 100 genes in the less vulnerable visual cortex region, which may be a critical component of the protection mechanism for less vulnerable brain regions. To facilitate the research in this field, we have provided the expression information of ~8000 relevant genes on a publicly accessible web server AlzBIG (http://alz.big.ac.cn).
