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Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of prodromal Alzheimer’s disease

GSE314950 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2026/01/12 Platform GPL34290
At a glance

RNA-seq (gene expression) · mouse · 14 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
14 samples: 14 samples, each with a distinct title — no replicated groupsGroups 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
Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's diseasebioRxiv : the preprint server for biology · 2026
Summary (written by the submitters)
Alzheimer’s disease (AD), though defined as a cognitive disorder, often presents neuropsychiatric symptoms such as anxiety, depression, agitation and sleep disruptions years before the onset of frank memory impairment. A hallmark prodromal feature is the accumulation of hyperphosphorylated “pretangle” tau (pTau) in the locus coeruleus (LC), the brain’s primary source of norepinephrine (NE), prior to any other region.
Read the full summary ↓
While clinical studies link LC tau burden to behavioral abnormalities, causal mechanisms remain unclear. We developed a translationally-relevant mouse model that recapitulates the ‘LC-first’ phenomenon observed in humans using cell type-specific viral expression of pathogenic P364S mutant human tau in LC neurons. Three months post-infusion, pTau accumulation coincided with anxiety- and compulsive-like behaviors and reduced sleep spindles without altering overall sleep architecture. Consistent with the behavioral phenotypes, electrophysiological recordings revealed significant increases in spontaneous and evoked LC activity, accompanied by astrocytic reactivity with no apparent neuronal death. Transcriptomic analysis identified upregulation of the pacemaker potassium/sodium channel Hcn2 in the LC, which may contribute to neuronal hyperexcitability. To further define molecular mechanisms linking pTau to behavioral and cellular phenotypes, we developed a cell type-specific proteomics approach, which revealed synaptic and metabolic alterations in LC neurons associated with tau pathology. Interestingly, early anxiety-like behaviors observed at 3 months diminished at later timepoints (6-9 months) and were replaced by anxiolytic phenotypes. These findings demonstrate that pTau triggers phenotypes reflective of LC-NE hyperactivity in the early stages of AD pathogenesis, laying the foundation for the development of LC-based disease-modifying targets to address neuropsychiatric manifestations.
Published in
Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease
Korukonda A, Blankenship HE, Kam K et al. · bioRxiv : the preprint server for biology 2026 · PMID 41659445 · doi:10.64898/2026.01.30.702923
This dataset
Open GSE314950 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 GSE314950_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 PRJNA1393387 and SRA study SRP657952. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41659445) ↗
Study design
14 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 14 sample titles: 14 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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