GEO series

Subtle changes in brain expression modules in Alzheimer’s disease TREM2 carriers compared to non-carriers

GSE140841 Homo sapiens (human) RNA-seq (gene expression) 133 samples Submitted 2025/10/04 Platform GPL18573

At a glance

RNA-seq (gene expression) · human · 133 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 133 samples
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Background: Rare heterozygous coding variants with a large effect on the risk of developing late-onset Alzheimer's disease (similar to ApoE4, OR 2.90-5.05) have been identified in the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) gene.

Read the full summary ↓

However, little is known about the mechanisms through which Trem2 maladjustment may lead to AD Methods: We performed differential expression and co-expression network analysis on samples obtained from 5 (mainly 2) brain areas from individuals carrying the TREM2 variant known to increase the risk of Alzheimer’s and others using RNA-Seq to obtain a systems level view of the effects of the TREM2 mutation Results: The absence of Trem2 has a stronger effect at an earlier age with the number of differential expressed (DE) genes being 17-fold greater at 4 months than at 8 months in cortex. By integrating DE genes and network analysis we discovered gene clusters associated with the disruption of blood vessel formation at 4 months of age and protein targeting primarily affecting the hippocampus at 8 months. Further integration of cell type and ontology information revealed a large disruption of a gene module enriched for endothelial cell markers coinciding with the module enriched for neuron cell markers having weaker connections to modules with oligodendrocyte and astrocyte identities. The module with neuronal identity has decreased expression only in the KO where it has closer association with a new module enriched for phagocytic functions Conclusions: Combining gene co-expression and differential expression analysis on brains of carriers of TREM2 mutations we demonstrate that the presence of damaging TREM2 mutation produce subtle disruptions.

This dataset

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Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE140841_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA591151 and SRA study SRP231430. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Samples in this study

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+ 133 more — browse all 133 samples with per-sample file links →

Datasets on a similar topic

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GSE284141 Increased APOE abundance in the brain in Down syndrome - Alzheimer’s disease compared with early onset-Alzheimer's disease is associated with elevated APP and C- terminal fragment abundance 16 samples shares alzheimer, compared
GSE285294 Cannabis Use and Cannabidiol Modulate HIV-Induced Alterations in TREM2 Expression: Implications for Age-Related Neuropathogenesis 48 samples shares trem2
GSE241858 iPSC-derived microglia carrying the TREM2 R47H/+ mutation are pro-inflammatory and promote synapse loss. 35 samples shares trem2
GSE293037 Bulk transcriptome analysis of wildtype, TREM2 knockout, GPR34 knock-out or TREM2/GPR34 double knock-out iPSC-derived human microglia treated either with PBS or myelin. 32 samples shares trem2

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