GEO series

Neuronal APOE4-induced Early Hippocampal Network Hyperexcitability in Alzheimer’s Disease Pathogenesis

GSE279550 Mus musculus (mouse) Single-nucleus RNA-seq 16 samples Submitted 2025/12/18 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 16 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 16 samples: 4 × SynCRE_E3_10M vs 4 × SynCRE_E3_5M vs 4 × SynCRE_E4_10M vs 4 × SynCRE_E4_5MGroups 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: Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesisNature aging · 2026

Summary (written by the submitters)

The full impact of apolipoprotein E4 (APOE4), the strongest genetic risk factor for Alzheimer's disease (AD), on neuronal and network function remains unclear. We found hippocampal region-specific network hyperexcitability in young APOE4 knock-in (E4-KI) mice which predicted cognitive deficits at old age. Network hyperexcitability in young E4-KI mice was mediated by hippocampal region-specific subpopulations of smaller and hyperexcitable neurons that were eliminated by selective removal of neuronal APOE4.

Read the full summary ↓

Aged E4-KI mice exhibited hyperexcitable granule cells, a progressive inhibitory deficit, and E/I imbalance in the dentate gyrus, exacerbating hippocampal hyperexcitability. Single-nucleus RNA-sequencing revealed neuronal cell type-specific and age-dependent transcriptomic changes, including Nell2 overexpression in E4-KI mice. Reducing Nell2 expression in specific neuronal types of E4-KI mice with CRISPRi rescued their abnormal excitability phenotypes, implicating Nell2 overexpression as a cause of APOE4-induced hyperexcitability. These findings highlight the early transcriptomic and electrophysiological alterations underlying APOE4-induced hippocampal network dysfunction and its contribution to AD pathogenesis with aging.

Published in

Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis

Tabuena DR, Jang SS, Grone B et al. · Nature aging 2026 · PMID 41933197 · doi:10.1038/s43587-026-01096-0

This dataset

Open GSE279550 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 GSE279550_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1173233 and SRA study SRP538755. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41933197) ↗

Study design

4 × SynCRE_E3_10M vs 4 × SynCRE_E3_5M vs 4 × SynCRE_E4_10M vs 4 × SynCRE_E4_5M

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 of them. 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

GSM8575010 SynCRE_E3_10M_1 SynCRE_E3_10M
GSM8575011 SynCRE_E3_5M_1 SynCRE_E3_5M
GSM8575012 SynCRE_E4_10M_1 SynCRE_E4_10M
GSM8575013 SynCRE_E4_5M_1 SynCRE_E4_5M
GSM8575014 SynCRE_E3_10M_2 SynCRE_E3_10M
GSM8575015 SynCRE_E3_5M_2 SynCRE_E3_5M
GSM8575016 SynCRE_E4_10M_2 SynCRE_E4_10M
GSM8575017 SynCRE_E4_5M_2 SynCRE_E4_5M
GSM8575018 SynCRE_E3_10M_3 SynCRE_E3_10M
GSM8575019 SynCRE_E3_5M_3 SynCRE_E3_5M
GSM8575020 SynCRE_E4_10M_3 SynCRE_E4_10M
GSM8575021 SynCRE_E4_5M_3 SynCRE_E4_5M
GSM8575022 SynCRE_E3_10M_4 SynCRE_E3_10M
GSM8575023 SynCRE_E3_5M_4 SynCRE_E3_5M
GSM8575024 SynCRE_E4_10M_4 SynCRE_E4_10M
GSM8575025 SynCRE_E4_5M_4 SynCRE_E4_5M

Datasets on a similar topic

GSE304212 Molecular Pathogenesis of Alzheimer's Disease Onset in a Mouse Model: Effects of Cannabidiol Treatment 60 samples shares pathogenesis, alzheimer
GSE333494 Hippocampal CA3 Nex+ neuronal TNFR2 alleviates chronic neuropathic pain by sex-dependently engaging opioid and endocannabinoid pathways 26 samples shares hippocampal, neuronal
GSE300348 Cdkn2a/p16INK4A Loss affects hippocampal transcription in Young Adult Mice Independently of Alzheimer ’s-Associated Genetic Pathways 23 samples shares hippocampal, alzheimer
GSE248275 Adenosine triggers early astrocyte reactivity that provokes microglial reaction and drives the pathogenesis of sepsis-associated encephalopathy 18 samples shares pathogenesis, early
GSE327604 Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer’s disease pathogenesis [RNA-Seq] 12 samples shares pathogenesis, alzheimer
GSE262422 Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Pathogenesis 12 samples shares pathogenesis, neuronal
GSE296390 p75 Neurotrophin Receptor Shapes the Dynamics of Adult Hippocampal Neurogenesis in Alzheimer's Disease 12 samples shares hippocampal, alzheimer
GSE247439 miRNA-mediated inhibition of an actomyosin network in hippocampal pyramidal neurons restricts sociability in adult male mice 12 samples shares hippocampal, network

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.