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Medium-chain triglycerides improve cognition and systemic metabolism in mouse models of Alzheimer's disease

GSE286571 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/08/11 Platform GPL19057
At a glance

RNA-seq (gene expression) · mouse · 24 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
24 samples: 6 conditions, mostly with about 4 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
Medium-chain triglycerides improve cognition and systemic metabolism in mouse models of Alzheimer's diseaseBrain : a journal of neurology · 2026
Summary (written by the submitters)
Lifestyle-based interventions, including dietary modifications, can reduce dementia risk. In this regard, dietary supplementation with medium-chain triglycerides (MCT) has shown potential therapeutic benefits in individuals with Alzheimer's disease (AD). These effects are widely presumed to be mediated by hepatic conversion of MCT into circulating ketones.
Read the full summary ↓
However, the physiological and cellular mechanisms underlying the benefits of MCT remain understudied, particularly in the context of AD. Here, we investigated the cellular and molecular changes occurring in the brain and systemically in response to dietary supplementation with MCT versus a ketogenic diet (KD). The experimental design consisted of comparing a 70% carbohydrate control diet to either a control diet supplemented with 10% MCT or a carbohydrate-free high fat KD. Diets were tested in two AD mouse models, slow-progressing 3xTg-AD mice that model pre-symptomatic/early stages and rapidly-progressing 5xFAD mice that model late stages of the disease. We found that MCT supplementation and KD both improved hippocampal-dependent spatial learning and memory, increased dendritic spine density of hippocampal neurons, and modulated hippocampal expression of genes associated with mitochondrial functions, synaptic structure, and insulin signaling in AD mouse models. However, unlike KD, MCT supplementation did not elevate circulating ketones, suggesting different mechanisms. Indeed, MCT enhanced the peripheral insulin response of AD mice, while KD conversely unveiled their latent metabolic vulnerability, increasing their hyperglycaemia, body weight gain, and adiposity. The systemic metabolic disturbances of AD mice correlated with transcriptomic alterations in hepatic lipid metabolism and ketogenesis genes and increased lipid droplet accumulation. These liver metabolic abnormalities were partially reversed by both MCT supplementation and KD, but in distinct ways. Notably, KD selectively triggered hepatic neutral lipid depletion and prominent proinflammatory gene expression while MCT down-regulated expression of cholesterol-related genes. Collectively, these findings reveal that MCT supplementation in the context of AD improves cognition and systemic metabolism without elevating circulating ketone levels.
Published in
Medium-chain triglycerides improve cognition and systemic metabolism in mouse models of Alzheimer's disease
M'Bra PEH, Hamilton LK, Moquin-Beaudry G et al. · Brain : a journal of neurology 2026 · PMID 40794774 · doi:10.1093/brain/awaf267
This dataset
Open GSE286571 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 GSE286571_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 PRJNA1209942 and SRA study SRP557026. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40794774) ↗
Study design
6 conditions, mostly with about 4 replicates each
Bulk_RNA-seq_Hippocampus, 3xTG, KD, n ×5 Bulk_RNA-seq_Hippocampus, 3xTG, M, n ×4 Bulk_RNA-seq_Hippocampus, WT, Control diet, n ×4 Bulk_RNA-seq_Hippocampus, WT, KD, n ×4 Bulk_RNA-seq_Hippocampus, WT, M, n ×4 Bulk_RNA-seq_Hippocampus, 3xTG, Control diet,… ×3

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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
Datasets on a similar topic

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