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Excitatory Neuronal ErbB4 Drives Early Pathophysiology of Alzheimer's Disease

GSE292137 Mus musculus (mouse) Single-nucleus RNA-seq 18 samples Submitted 2025/11/25 Platform GPL24247
At a glance

Single-nucleus RNA-seq · mouse · 18 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
18 samples: 7 conditions, mostly in triplicateGroups 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.
Summary (written by the submitters)
Neuroinflammation and synapse loss synergistically contribute to cognitive decline in Alzheimer’s disease (AD). Although microglial hyper-phagocytic activity has been shown to mediate synapse loss, the exact mechanisms underlying these pathologies remain obscure. Here, we first demonstrate that astrocytes and microglia increase the phagocytic elimination of excitatory synapses, but significantly decrease their elimination of inhibitory synapses during AD progression, suggesting neuroinflammation may be dispensable for early AD synapse loss.
Read the full summary ↓
Instead, through single-nucleus RNA sequencing (snRNAseq), we identified Disease-Initiating Excitatory Neurons (DIENs), characterized by ectopic Erbb4 expression, as the earliest alteration in an AD mouse model. Notably, specific deletion of Erbb4 in 5XFAD excitatory neurons abrogated abnormal neuro-network activities and synapse loss, as well as reactive gliosis, amyloid plaque deposition, and cognitive deficits. Conversely, overexpression of Erbb4 in wild-type excitatory neurons recapitulated key AD phenotypes, including cognitive impairment. Subsequent snRNAseqs following Erbb4 deletion and overexpression confirm that excitatory neuronal Erbb4 is both sufficient and necessary to induce DIEN and reactive gliosis. Together, these findings reveal that the early pathophysiology of AD arises largely due to aberrant Erbb4 expression in excitatory neurons, and that targeting excitatory neuronal Erbb4 may thus represent a novel therapeutic strategy for mitigating AD progression.
This dataset
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.

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 GSE292137_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1237264 and SRA study SRP570904. Searching any of these in the dataset finder brings you back here.

Study design
7 conditions, mostly in triplicate
Hippocampal CA1 of 4m_sgControl_5XFAD ×3 Hippocampal CA1 of 4m_sgErbb4_5XFAD ×3 Hippocampal CA1 of 4m_HA_WT ×3 Hippocampal CA1 of 4m_Erbb4_WT ×3 Hippocampus of 2m_5XFAD ×2 Hippocampus of 3m_WT ×2 Hippocampus of 3m_5XFAD ×2

Supports a between-group comparison across 18 samples.

How we read this: 7 replicated groups read from 18 sample titles; they account for 18 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
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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.