title: Robust gene dysregulation in Alzheimer's disease brains.
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).
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Feng
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhouxian
authors.initials: Z
authors.lastname: Bai
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Jiya
authors.initials: J
authors.lastname: Sun
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Guangchun
authors.initials: G
authors.lastname: Han
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Fuhai
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Crack
authors.affiliation: UC Davis Genome Center and Department of Biomedical Engineering, Davis, CA, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Duan
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China UC Davis Genome Center and Department of Biomedical Engineering, Davis, CA, USA Center of Alzheimer's disease, Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Lei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D059467:Transcriptome
keywords: Brain transcriptome; disease progression; gene expression; transcriptional “cushion”