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SEX-DEPENDENT APOE4 NEUTROPHIL-MICROGLIA INTERACTIONS DRIVE COGNITIVE IMPAIRMENT IN ALZHEIMER'S DISEASE [Human_F_M_HC_MCI_AD_E33_34]

GSE243743 Homo sapiens (human) RNA-seq (gene expression) 94 samples Submitted 2024/06/04 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 94 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
94 samples: 94 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
Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's diseaseNature medicine · 2024
Summary (written by the submitters)
APOE4 is the strongest genetic risk factor for Alzheimer's disease (AD) with increased odds ratios in females. Targeting amyloid plaques show modest improvement in male non-APOE4 carriers. Leveraging transcriptomics across APOE variants in both sexes, multiplex flow cytometry and validation in two independent cohorts of APOE4 female AD patients, we identify a new subset of neutrophils associated with cognitive impairment.
Read the full summary ↓
This phenotype is defined by increased IL-17 and IL-1 co-expressed gene modules in blood neutrophils of cognitively impaired female APOE e4 carriers, showing increased infiltration to the AD brain. APOE4 female IL-17+ neutrophils upregulated the immunosuppressive cytokines IL-10 and TGFb, and immune checkpoints including LAG-3 and PD-1, associated with accelerated immune aging. Deletion of APOE4 in neutrophils reduced this immunosuppressive phenotype and restored microglial response to neurodegeneration (MGnD), limiting plaque pathology in AD mice. Mechanistically, IL-17Fupregulated in APOE4 neutrophils interacts with microglial IL-17RA to suppress the induction of MGnD phenotype, and blocking this axis supported cognitive improvement in AD mice. These findings provide a translational basis to target IL-17F in APOE e4 female carriers with cognitive impairment.
Published in
Sex-dependent APOE4 neutrophil-microglia interactions drive cognitive impairment in Alzheimer's disease
Rosenzweig N, Kleemann KL, Rust T et al. · Nature medicine 2024 · PMID 38961225 · doi:10.1038/s41591-024-03122-3
This dataset
Open GSE243743 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 GSE243743_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 PRJNA1019745 and SRA study SRP462556. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38961225) ↗
Study design
94 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 94 sample titles: 94 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

+ 54 more — browse all 94 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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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.