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Series GSE127884 Query DataSets for GSE127884
Status Public on Apr 23, 2019
Title The major risk factors for Alzheimer’s disease: Age, Sex and Genes, modulate the microglia response to Aβ plaques (CDEP)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Microglia are involved in Alzheimer’s disease (AD) by adopting activated phenotypes. How ageing in the absence or presence of β-amyloid (Aβ) deposition in different brain areas affects this response and whether sex and AD risk genes are involved, remains however largely unknown. Here we analyzed the gene expression profiles of more than 10,000 individual microglia cells isolated from cortex and hippocampus of male and female AppNL-G-F at 4 different stages of Aβ deposition and in age-matched control mice. We demonstrate that microglia adopt two major activated states during normal aging and after exposure to amyloid plaques. One of the responses (activated response microglia, ARM) is enhanced in particular by amyloid plaques and is strongly enriched with AD risk genes. The ARM response is not homogeneous, as subgroups of microglia overexpressing MHC type II and tissue repair genes (Dkk2, Gpnmb, Spp1) are induced upon prolonged Aβ exposure. Microglia in female mice advance faster in the activation trajectories. Similar activated states were also found in a second AD model and in human brain. We demonstrate that abolishing the expression of Apoe, the major genetic risk factor for AD, impairs the establishment of ARMs, while the second microglia response type, enriched for interferon response genes, remains unaffected. Our data indicate that ARMs are the converging point of multiple AD risk factors.
 
Overall design RNA-Seq of cortical and hippocampal microglia in male APP/PS1-Apoe(null), APP/PS1, C57Bl/6 and C57Bl/6-Apoe(null) mice ; at month 18
 
Contributor(s) Frigerio CS, Wolfs L, Fattorelli N, Thrupp N, Voytyuk I, Schmidt I, Mancuso R, Chen W, Woodbury M, Srivastava G, Möller T, Hudry E, Das S, Saido T, Karran E, Hyman B, Perry VH, Fiers M, De Strooper B
Citation(s) 31018141
Submission date Mar 05, 2019
Last update date Apr 29, 2019
Contact name Bart de Strooper
E-mail(s) bart.destrooper@kuleuven.be
Organization name KULeuven
Department VIB-KU Leuven Center for Brain & Disease Research
Street address Campus Gasthuisberg, Herestraat 49, bus 602
City Leuven
ZIP/Postal code 3000
Country Belgium
 
Platforms (1)
GPL21626 NextSeq 550 (Mus musculus)
Samples (3072)
GSM3640488 D18MC.1A1
GSM3640489 D18MC.1A10
GSM3640490 D18MC.1A11
This SubSeries is part of SuperSeries:
GSE127893 The major risk factors for Alzheimer’s disease: Age, Sex and Genes, modulate the microglia response to Aβ plaques
Relations
BioProject PRJNA525702
SRA SRP187600

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
GSE127884_microglia.cdep.SeuratNorm.tsv.gz 37.6 Mb (ftp)(http) TSV
GSE127884_microglia.cdep.meta.csv.gz 25.2 Kb (ftp)(http) CSV
GSE127884_microglia.cdep.raw.tsv.gz 9.3 Mb (ftp)(http) TSV
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Raw data are available in SRA
Processed data are available on Series record

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