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APOE3-R136S mutation confers resilience against tau pathology via cGAS-STING-IFN inhibition [bulk RNA-seq]

GSE297743 Mus musculus (mouse) RNA-seq (gene expression) 28 samples Submitted 2025/06/15 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 28 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
Mus musculus (mouse)
Samples
28 samples: 19 distinct titles, 2 of them repeatedGroups are read from the sample names, not from the paper. Check the list below.
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.
Paper
The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathwayImmunity · 2025
Summary (written by the submitters)
The Christchurch mutation (R136S) on the APOE3 (E3S/S) gene is associated with attenuation of tau load and cognitive decline despite the presence of a causal PSEN1 mutation and high levels of amyloid beta pathology in the carrier. However, the specific molecular mechanisms enabling the E3S/S mutation to mitigate tau-induced neurodegeneration remain unclear.
Read the full summary ↓
Here, we replaced mouse ApoE with wild-type human E3 or E3S/S on a tauopathy background. The R136S mutation markedly decreased tau load and protected against tau-induced synaptic loss, myelin loss, and reduction in theta and gamma powers. Additionally, the R136S mutation reduced interferon response to tau pathology in both mouse and human microglia, suppressing cGAS-STING activation. Treating tauopathy mice carrying wild-type E3 with a cGAS inhibitor protected against tau-induced synaptic loss and induced similar transcriptomic alterations to those induced by the R136S mutation across brain cell types. Thus, suppression of microglial cGAS-STING-IFN pathway plays a central role in mediating the protective effects of R136S against tauopathy.
Published in
The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS-STING-IFN pathway
Naguib S, Lopez-Lee C, Torres ER et al. · Immunity 2025 · PMID 40555238 · doi:10.1016/j.immuni.2025.05.023
This dataset
Open GSE297743 in finder → Find more mouse RNA-seq datasets →
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 GSE297743_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 PRJNA1266081 and SRA study SRP586794. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40555238) ↗
Study design
19 distinct titles, 2 of them repeated
E3 ×6 E3CC ×5

How we read this: Read from 28 sample titles: 19 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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