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Targeting microglial phosphatidylethanolamine synthesis pathway promotes GABARAP-associated phagocytosis and A clearance in Alzheimer's disease

GSE327618 Mus musculus (mouse) RNA-seq (gene expression) 9 samples Submitted 2026/07/22 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 9 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
9 samples: 3 × RNA-seq of QA-injected 5xFAD mouse hippocampus vs 3 × RNA-seq of vehicle-injected 5xFAD mouse hippocampus vs 3 × RNA-seq of vehicle-injected WT mouse hippocampusGroups 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
Targeting the microglial phosphatidylethanolamine synthesis pathway promotes GABARAP-associated phagocytosis and Aβ clearance in Alzheimer's diseaseSignal transduction and targeted therapy · 2026
Summary (written by the submitters)
Alzheimer’s disease (AD) is a major cause of dementia and a prevalent age-related neurodegenerative disorder, characterized by progressive cognitive impairment and memory loss. Although metabolic activation or dysfunction of microglia is implicated in AD pathogenesis, the phospholipid metabolism–associated signaling mechanisms within microglia remain poorly defined.
Read the full summary ↓
In this study, we demonstrate that quinolinic acid (QA), a byproduct of tryptophan catabolism via the kynurenine pathway, activates the microglial Kennedy pathway—responsible for de novo phosphatidylethanolamine (PE) biosynthesis—by upregulating the enzymes EPT1 and ETNK1. This activation markedly enhances the synthesis of PE species enriched in polyunsaturated fatty acids. Concurrently, QA significantly increases the expression of gamma-aminobutyric acid receptor–associated protein (GABARAP), promotes its lipidation, and facilitates GABARAP-associated phagocytosis (GAP) of Aβ oligomers by microglia. Knockdown of EPT1 and ETNK1 attenuated QA-induced PE synthesis and impaired GAP of Aβ oligomers, while inhibition of GABARAP lipidation via STBD1-deconjugase substantially reduced QA-mediated GAP. QA administration upregulated microglial Gabarap expression and decreased Aβ plaque burden in the hippocampus of AD (5xFAD) mice, whereas Gabarap knockdown abrogated QA-induced microglial clearance of Aβ. Collectively, these findings reveal a paradoxically beneficial role of QA in activating a microglia-specific signaling cascade that promotes PE biosynthesis and GAP, thereby enhancing Aβ clearance and mitigating AD pathology. Targeting the microglial PE synthesis pathway and GAP may represent a promising therapeutic strategy to ameliorate Aβ accumulation and slow AD progression
Published in
Targeting the microglial phosphatidylethanolamine synthesis pathway promotes GABARAP-associated phagocytosis and Aβ clearance in Alzheimer's disease
Hyeon SJ, Kim SC, Chu J et al. · Signal transduction and targeted therapy 2026 · PMID 42457676 · doi:10.1038/s41392-026-02789-z
This dataset
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.

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 GSE327618_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1415460 and SRA study SRP671146. Searching any of these in the dataset finder brings you back here.

Study design
3 × RNA-seq of QA-injected 5xFAD mouse hippocampus vs 3 × RNA-seq of vehicle-injected 5xFAD mouse hippocampus vs 3 × RNA-seq of vehicle-injected WT mouse hippocampus

Supports a between-group comparison across 9 samples.

How we read this: 3 replicated groups read from 9 sample titles; they account for 9 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
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