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Series GSE173955 Query DataSets for GSE173955
Status Public on Dec 23, 2021
Title Integrative analysis of altered genes expressed in human Alzheimer’s disease brain (RNA-Seq)
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary We had previously performed comparative gene expression profiling of human postmortem Alzheimer’s disease (AD) brains donated for the Hisayama study. The hippocampi from AD brains showed the most significant alteration in gene expression profile [PMID: 23595620]. In the present study, in order to identify molecular pathological alterations in AD hippocampus, we applied human transcriptome array and RNA-sequencing to the same samples and reanalyzed the gene array data, and performed integrative analysis of all 3 methods. We also applied gene array to hippocampus of 6-month-old AppNL-G-F/NL-G-F knock-in AD model mice as a preclinical AD stage model, and at last we performed the interspecies comparison. Functional annotation clustering with the results of all 3 or at least 2 methods in human, showed synapse, cell junction, calmodulin binding, ion transport and glycoproteins as the top affected terms. In hippocampi of AppNL-G-F/NL-G-F mice which exhibit significant amyloidosis but not neuronal degeneration, we found that expression of genes categorized in signaling specially signaling peptides with disulfide bond or glycoproteins, together with the innate immune response and lysosome of cells are upregulated. Comparing the extended human data with mouse data, we found and confirmed by qRT-PCR, 2 common up-regulated genes, Clec7a and C4b, which induce innate immune response and synapse elimination. We also found and confirmed by qRT-PCR, 2 common down-regulated genes, one is Slc17a6, which can affect synaptic transmission of glutamate, and second one is Rxfp1, which is involved in gene transcription. Amyloid-𝛽 accumulation is the major hallmark of AD at 6 month-old AppNL-G-F/NL-G-F mice, therefore our data suggests that amyloid-𝛽 accumulation induces innate immune response, synapse elimination, besides it can decreases glutamate transmission, and affect gene transcription in early stage of hippocampal AD brain, prior to neuronal degeneration.
 
Overall design We analyzed postmortem human hippocampus brains from 8 AD and 10 non-AD subjects using Illumina TruSeq stranded mRNA LT Sample Prep kit. Sequences were obtained by using HiSeq1500. One AD and one non-AD sample applied two independent times to sequencer in order to obtain more reads.
 
Contributor(s) Abolhassani N, Nakabeppu Y
Citation(s) 34970419
Submission date May 05, 2021
Last update date Jan 10, 2022
Contact name Yusaku Nakabeppu
E-mail(s) yusaku@bioreg.kyushu-u.ac.jp
Phone 81-92-642-6800
Organization name Medical Institute of Bioregulation, Kyushu University
Department Department of Immunobiology and Neuroscience
Lab Division of Neurofunctional Genomics
Street address 3-1-1 Maidashi Higashi-ku
City Fukuoka
State/province Fukuoka
ZIP/Postal code 812-8582
Country Japan
 
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (18)
GSM5283449 Alzheimer's Disease_Biological replicate 1
GSM5283450 Alzheimer's Disease_Biological replicate 2
GSM5283451 Alzheimer's Disease_Biological replicate 3
Relations
BioProject PRJNA727602
SRA SRP318632

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
GSE173955_Table_1_gene_level_expression.xlsx 14.0 Mb (ftp)(http) XLSX
GSE173955_Table_2_known_transcripts.xlsx 25.9 Mb (ftp)(http) XLSX
GSE173955_Table_3_unknown_transcripts.xlsx 12.1 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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