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Series GSE29378 Query DataSets for GSE29378
Status Public on Jun 07, 2013
Title Genes and Pathways Underlying Regional and Cell Type Changes in Alzheimer's Disease
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Along with the two hallmark pathologies—intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques—transcriptional studies suggest that Alzheimer's disease (AD) results from dysfunction of many cellular pathways including synaptic transmission, cytoskeletal dynamics, and apoptosis. While these studies consistently point to the same pathways involved in AD, there is no consensus on which genes in each pathway are disease-relevant, much less on whether these genes play causative roles or are downstream effects of disease progression. To address these issues, we have performed a large-scale transcriptional analysis in brain of individuals with advanced AD and non-demented controls, focusing specifically on CA1 and the relatively less affected CA3. For comparisons between regions and across disease status, we find consistency in both pathway enrichment as well as specific differentially expressed genes across several studies. Furthermore, genes that show decreased expression with AD progression also tend to show enrichment in CA3 (and vice versa), suggesting that transcription levels in a region may reflect that region's vulnerability to disease. In particular, we find several strong candidate vulnerability (ABCA1, MT1H, PDK4, RHOBTB3) and protection (FAM13A1, LINGO2, UNC13C) genes based on expression patterns. We have also applied weighted gene coexpression network analysis (WGCNA) to explore the pathophysiology of AD from a systems perspective, finding modules for major cell types, which each show distinct disease-relevant expression patterns. In particular, a microglial module shows increased expression in the brain of non-demented controls harboring early NFT pathology, suggesting that microglial activation is an early event in AD progression.
 
Overall design Total RNA obtained from 60um sections of frozen human hippocampus was collected using scalpel dissection. Control and AD brains were matched for all non-disease characteristics as closely as possible. CA1 and CA3 dissections for a given individual were taken from the same section. Several region- and disease-related comparisons were performed.
 
Contributor(s) Miller JA, Woltjer RL, Goodenbour JM, Horvath S, Geschwind DH
Citation(s) 23705665, 37485875
Submission date May 18, 2011
Last update date Sep 14, 2023
Contact name Jeremy Miller
E-mail(s) jeremyinla@gmail.com
Organization name Allen Institute for Brain Science
Street address 615 Westlake Ave N
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (1)
GPL6947 Illumina HumanHT-12 V3.0 expression beadchip
Samples (63)
GSM726083 AD - #4147 - hippocampus CA3 - Male - 66yr
GSM726084 Control - #1385 - hippocampus CA3 - Male - 81yr
GSM726085 Control - #3795 - hippocampus CA1 - Female - 72yr
Relations
BioProject PRJNA140105

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE29378_RAW.tar 6.2 Mb (http)(custom) TAR
GSE29378_non-normalized.txt.gz 22.2 Mb (ftp)(http) TXT
Processed data included within Sample table
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