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Paired Vascular-Parenchymal Single Nuclei Sequencing Reveals Perturbed Endothelial-to-Mesenchymal Transition in Alzheimer’s Disease

GSE310554 Homo sapiens (human) Single-nucleus RNA-seq 39 samples Submitted 2025/11/28 Platform GPL24676
At a glance

Single-nucleus RNA-seq · human · 39 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
39 samples: 10 × Parenchymal fraction, Control, dono vs 10 × Vascular fraction, Control, dono vs 10 × Vascular fraction, AD, dono vs 9 × Parenchymal fraction, AD, donoGroups 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)
The neurovascular unit (NVU) plays a crucial role in maintaining brain functions by integrating vascular cells, neurons, and glia to ensure metabolic support and blood-brain barrier integrity. While vascular dysfunction has been implicated in Alzheimer's disease (AD), the specific contributions of various vascular cell types remain understudied, partly due to challenges in isolating these cells from post-mortem tissue.
Read the full summary ↓
In this study, we analyzed prefrontal cortex tissue from AD patients and control subjects using single-nuclei RNA sequencing to create a high-resolution atlas capturing major vascular and parenchymal cell types. Our findings reveal distinct associations between AD risk and gene expression profiles specific to pericytes, perivascular fibroblasts, and activated microglia. Functional analyses indicate that these genes converge on amyloid-related pathways, suggesting that perivascular compartments and immune modulators play significant roles in the early stages of AD pathobiology. Additionally, we identified a new endothelial-mesenchymal transition population that is diminished in AD, indicating a potential disruption in endothelial plasticity that may contribute to vascular dysfunction. Key ligand-receptor interactions between vascular and parenchymal cell types, such as ANGPT2, were found to be markedly dysregulated, highlighting potential targets that could drive NVU breakdown in AD. These findings provide a comprehensive framework for evaluating NVU cells in human disease and underscore novel links between vascular dynamics and AD pathogenesis. The study offers valuable insights into disease mechanisms and suggests new therapeutic avenues aimed at protecting and restoring the brain's neurovascular interface.
This dataset
Open GSE310554 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 GSE310554_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1307833 and SRA study SRP609813. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
10 × Parenchymal fraction, Control, dono vs 10 × Vascular fraction, Control, dono vs 10 × Vascular fraction, AD, dono vs 9 × Parenchymal fraction, AD, dono

Supports a between-group comparison across 39 samples.

How we read this: 4 replicated groups read from 39 sample titles; they account for 39 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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