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High throughput screening of patient's iPSC-derived neurons identifies gut microbial metabolites as a potential treatment for Alzheimer's disease.

GSE295280 Homo sapiens (human) RNA-seq (gene expression) 11 samples Submitted 2025/04/23 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 11 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
Homo sapiens (human)
Samples
11 samples: 3 × Brain organoids, Agmatine 100 µM, Day 1 vs 3 × Brain organoids, DMSO, Day 3 vs 3 × Brain organoids, Agmatine 100 µM, Day 3 vs 2 × Brain organoids, DMSO, Day 1Groups 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)
Altered gut microbial composition observed in Alzheimer’s disease patients drive microbial metabolome changes associated with AD pathogenesis; however, key microbial metabolites involved in this process and their functional roles are unknown. Here, we screened library of 352 gut metabolites in AD patient iPSC derived neurons for their ability to reduce phosphorylation of tau.
Read the full summary ↓
We identified 4-methylcatechol, menaquinone-4 and agmatine as candidate metabolites associated with decreased tau phosphorylation and chose agmatine for further validatory studies. We demonstrated that Agmatine significantly reduce tau hyperphosphorylations (pTau181, pTau205 and pTau231) in AD patient iPSC-derived neurons and cerebral organoids. We also observed that agmatine treatment enhances learning and memory, reduces amyloid burden and neuroinflammation in a 5xFAD mouse model. Transcriptomics analysis from patient iPSC derived brain organoids suggested decreased expression of complement system pathway genes (e.g. C1S, C2, C3AR1, C5AR1) by agmatine treatment. The study also highlights agmatine as an important modulator of AD pathology via regulating C3aR-STAT3 axis and implicates it as a novel therapeutic target for AD.
This dataset
Open GSE295280 in finder → Find more human 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 GSE295280_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 PRJNA1254111 and SRA study SRP580429. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × Brain organoids, Agmatine 100 µM, Day 1 vs 3 × Brain organoids, DMSO, Day 3 vs 3 × Brain organoids, Agmatine 100 µM, Day 3 vs 2 × Brain organoids, DMSO, Day 1

Supports a between-group comparison across 11 samples.

How we read this: 4 replicated groups read from 11 sample titles; they account for 11 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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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.