Excel · study · 2026
HDL-mimetic peptide treatment reverses APOE4-induced transcriptomic and lipidomic alterations in the brain of humanized APOE mice
Listed in NCBI GEO
INTRODUCTION: The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD).
Description
APOE4 has reduced lipidation capacity and impaired lipid transport, disrupting neuronal maintenance. The high-density lipoprotein (HDL)-mimetic peptide 4F offers a potential therapeutic strategy.
METHODS: To investigate how APOE4 alters brain gene expression and lipid metabolism and to evaluate the therapeutic potential of 4F, we performed dual-omics analysis in APOE4/4 (E4/4) and APOE3/3 (E3/3) mice treated intraperitoneally with D-enantiomer of 4F (D4F) or vehicle for 12 weeks to 13 months of age. RESULTS: APOE4/4 mice showed widespread transcriptomic and lipidomic alterations, including downregulation of lipid metabolism and synaptic pathways, increased ceramides, sphingomyelins, and cholesteryl esters, and decreased triglycerides and diglycerides.
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D4F treatment restored gene expression and lipid profiles toward APOE3/3 levels. DISCUSSION: These findings reveal molecular mechanisms underlying APOE4-driven dysregulation and support the therapeutic potential of HDL-mimetic peptides to mitigate APOE4-associated alterations in AD.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE307nnn/GSE307255 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307255 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1315028 ncbi.nlm.nih.gov/bioproject/PRJNA1315028 ↗
project · from NCBI GEO
- PubMed 42337953 pubmed.ncbi.nlm.nih.gov/42337953 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE307255 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |