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Perimenopausal State Oestradiol to Progesterone Imbalance Drives Alzheimer’s Risk via ERRα Dysregulation and Energy Dyshomeostasis

GSE279885 Mus musculus (mouse) RNA-seq (gene expression) 59 samples Submitted 2025/10/23 Platform GPL24247Platform GPL21273
At a glance

RNA-seq (gene expression) · mouse · 59 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
59 samples: 10 conditions, mostly with about 8 replicates eachGroups 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
Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasisNature communications · 2025
SuperSeries — this record groups several sub-series.
Summary (written by the submitters)
This SuperSeries is composed of the SubSeries listed below. Sex-biased differences in Alzheimer’s disease (AD) are well documented, but the mechanisms underlying increased vulnerability in postmenopausal women remain unclear. This study aimed to model the effects of perimenopausal hormonal fluctuations on AD pathophysiology. Using a VCD-induced accelerated ovarian failure model in young female C57BL/6J and 3xTg mice, we simulated a perimenopausal state with hormonal changes characterized by elevated oestradiol levels and reduced progesterone levels.
Read the full summary ↓
Supporting human brain transcriptomic and metabolomic data from the ROSMAP study revealed that impaired oestrogen-related receptor alpha (ERRα) function was a key driver of female sex-biased vulnerability. In female mice, progesterone-guided oestrogen receptor signalling maintained ERRα activity by regulating neuronal cholesterol homeostasis and the TCA cycle. Hormonal imbalances disrupted this mechanism, triggering an aspartate-driven “minicycle,” which increased glutamate release, neuronal excitability, ATP depletion, and energy crisis susceptibility. This study demonstrates how perimenopausal hormonal imbalances exacerbate AD risk via ERRα dysfunction, linking neuronal cholesterol and energy homeostasis to disease vulnerability.
Published in
Perimenopausal state oestradiol to progesterone imbalance drives Alzheimer's risk via ERRα dysregulation and energy dyshomeostasis
Sun JK, Peng AZ, Hart RP et al. · Nature communications 2025 · PMID 41274899 · doi:10.1038/s41467-025-66726-4
This dataset
Open GSE279885 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 GSE279885_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 PRJNA1175037 and SRA study SRP510531. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41274899) ↗
Study design
10 conditions, mostly with about 8 replicates each
EnrichedNeuron_Esrra_shRNA ×8 EnrichedNeuron_Scrambled_shRNA ×8 3xTg female mice, treated with vehicle contro… ×6 3xTg female mice, treated with vehicle contro… ×6 3xTg female mice, treated with P4 in Cycle 14… ×5 3xTg female mice, treated with VCD in Cycle 1… ×5 C57BL/6 female mice, treated with VCD, biolog… ×4 3xTg female mice, treated with VCD, biologica… ×4 +9 more

Supports a case/control comparison: 18 samples read as cases, 12 as controls.

How we read this: 10 replicated groups read from 59 sample titles; they account for 52 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

+ 19 more — browse all 59 samples with per-sample file links →

Datasets on a similar topic

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