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The HDL-Mimetic Peptide 4F Mitigates Vascular and Cortical Amyloid Pathology and Associated Neuroinflammation in a Transgenic Mouse Model of Cerebral Amyloid Angiopathy and Alzheimer’s Disease

GSE271286 Mus musculus (mouse) RNA-seq (gene expression) 15 samples Submitted 2025/03/24 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 15 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: 15 samples: 6 conditions, mostly in triplicateGroups 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: The HDL-Mimetic Peptide 4F Mitigates Vascular and Cortical Amyloid Pathology and Associated Neuroinflammation in a Transgenic Mouse Model of Cerebral Amyloid Angiopathy and Alzheimer's DiseaseMolecular neurobiology · 2025

Summary (written by the submitters)

Alzheimer's disease (AD) is the most common cause of age-related dementia worldwide with limited effective treatments. Cerebral amyloid angiopathy (CAA) is one of the key pathological hallmarks of AD characterized by amyloid-β (Aβ) deposition in the cerebral vasculature and is associated with intracerebral hemorrhage, cerebrovascular dysfunction, and cognitive impairment.

Read the full summary ↓

CAA is also considered to underlie the main adverse effect of anti-Aβ immunotherapies, the amyloid-related imaging abnormalities (ARIA). Substantial evidence from clinical and animal studies has shown that elevated levels of high-density lipoprotein (HDL), and its main protein component, apolipoprotein (APO) A-I, are associated with reduced CAA and superior cognitive function. 4F is an APOA-I/HDL-mimetic peptide that has advanced into clinical trials for cardiovascular diseases. The present study aimed to investigate whether treatment with the HDL mimetic peptide 4F modulates CAA and associated cognitive deficits and neuropathologies in the well-established transgenic Tg-SwDI mouse model of CAA/AD. Age- and sex-matched Tg-SwDI mice received daily treatments of 4F or vehicle (PBS), respectively, by intraperitoneal injections for 12 weeks. The results showed that the 4F treatment reduced CAA as well as overall Aβ plaque deposition, and attenuated microgliosis associated with CAA. Unbiased brain transcriptomic analysis revealed a heightened inflammatory state in the brain of SwDI mice, and that 4F treatment reversed the overactivation of vascular cells, in particular vascular smooth muscle cells, relieving cerebrovascular inflammation in CAA/AD mice. Our study provides experimental evidence for the therapeutic potential of 4F to mitigate CAA and its associated pathogenic processes in AD, including ARIA.

Published in

The HDL-Mimetic Peptide 4F Mitigates Vascular and Cortical Amyloid Pathology and Associated Neuroinflammation in a Transgenic Mouse Model of Cerebral Amyloid Angiopathy and Alzheimer's Disease

Zhong R, Chernick D, Hottman D et al. · Molecular neurobiology 2025 · PMID 40120042 · doi:10.1007/s12035-025-04859-9

This dataset

Open GSE271286 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 GSE271286_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 PRJNA1130861 and SRA study SRP517500. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40120042) ↗

Study design

6 conditions, mostly in triplicate

SwDI PBS M ×3 SwDI D4F F ×3 SwDI D4F M ×3 SwDI PBS F ×2 B6WT F ×2 B6WT M ×2

Supports a between-group comparison across 15 samples.

How we read this: 6 replicated groups read from 15 sample titles; they account for 15 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

GSM8373007 SwDI PBS F1 SwDI PBS F
GSM8373008 SwDI PBS F2 SwDI PBS F
GSM8373009 SwDI PBS M1 SwDI PBS M
GSM8373010 SwDI PBS M2 SwDI PBS M
GSM8373011 SwDI PBS M3 SwDI PBS M
GSM8373012 SwDI D4F F1 SwDI D4F F
GSM8373013 SwDI D4F F2 SwDI D4F F
GSM8373014 SwDI D4F F3 SwDI D4F F
GSM8373015 SwDI D4F M1 SwDI D4F M
GSM8373016 SwDI D4F M2 SwDI D4F M
GSM8373017 SwDI D4F M3 SwDI D4F M
GSM8373018 B6WT F1 B6WT F
GSM8373019 B6WT F2 B6WT F
GSM8373020 B6WT M1 B6WT M
GSM8373021 B6WT M2 B6WT M

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