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Distinct effects of restricting individual branched-chain amino acids on the development and progression of Alzheimer’s disease in 3xTg mice

GSE299928 Mus musculus (mouse) RNA-seq (gene expression) 47 samples Submitted 2025/07/30 Platform GPL16417
At a glance

RNA-seq (gene expression) · mouse · 47 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
47 samples: 47 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
Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg MiceAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
Summary (written by the submitters)
Dietary protein is a critical regulator of metabolic health and aging in diverse species, and many of the benefits of low-protein diets are recapitulated by restriction of the three branched-chain amino acids (BCAAs), leucine, isoleucine, and valine. In mouse models of Alzheimer’s disease (AD), dietary supplementation with BCAAs worsens AD neuropathology, while restriction of any of the BCAAs improves cognitive deficits.
Read the full summary ↓
We recently discovered that each BCAA has distinct metabolic effects, with the restriction of isoleucine alone being sufficient to improve metabolic health and extend lifespan and healthspan in genetically diverse mice. Here, we investigate the effect of restricting each individual BCAA on metabolic health and the development and progression of AD in the 3xTg mouse model. We find that restriction of isoleucine and valine, but not leucine, promotes metabolic health. Restricting any of the three BCAAs improved short-term memory in males, with isoleucine restriction having the strongest effect, while restricting valine has the greatest cognitive benefits in females. Restriction of each BCAA had distinct effects on AD pathology, mTOR signaling, autophagy, and survival. Transcriptomic analysis of the brain revealed both distinct and shared, and highly sex-specific, molecular impacts of restricting each BCAA, and we identify a set of significantly altered pathways strongly associated with reduced AD pathology and improved cognitive performance in males. Our findings suggest that restricting any of the BCAAs, particularly isoleucine or valine, may form the basis of a novel sex-specific approach to prevent or delay the progression of AD.
Published in
Restriction of Individual Branched-Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice
Babygirija R, Green CL, Sonsalla MM et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2026 · PMID 41817439 · doi:10.1002/advs.202515220
This dataset
Open GSE299928 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 GSE299928_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 PRJNA1277340 and SRA study SRP592608. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41817439) ↗
Study design
47 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 47 sample titles: 47 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

+ 7 more — browse all 47 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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