Excel · study · 2026
Repurposing Trazodone for Alzheimer's Disease to Modulate Soluble ST2 Levels and Alleviate Alzheimer's Pathology
Listed in NCBI GEO
Alzheimer’s disease (AD) is a multifactorial disorder involving various pathological mechanisms, such as amyloidosis, immune dysfunctions and synaptic impairments, which are important therapeutic targets.
Description
Repurposing drugs to target these mechanisms offers a promising approach to reduce the costs and duration of drug development. Notably, genetic studies underscore the role of microglial clearance of amyloid-beta (Aβ) in AD pathogenesis, with soluble ST2 (sST2) identified as a disease-modifying factor that impairs microglial clearance functions.
In this study, we investigated drug repurposing opportunities to modulate sST2 levels and alleviate AD pathologies. Unbiased screening of common medications in AD patients and validation in model systems identified trazodone, an anti-depressant used to treat major depressive disorder, as a leading negative regulator of sST2. Trazodone primarily regulates sST2 expression through its antagonistic effects on adrenergic signaling.
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Importantly, trazodone treatment enhanced microglial interaction with Aβ and alleviated Aβ pathology in the APP/PS1 transgenic mouse model of AD. Furthermore, trazodone treatment reduced neurodegeneration and rescued synaptic deficits in APP/PS1 mice. Comprehensive molecular profiling of APP/PS1 mouse brains showed that trazodone restores the expression of synaptic proteins involved in synaptic integrity and plasticity.
Collectively, these findings demonstrate that trazodone is a promising repurposing agent for AD that targets the underlying immune dysfunctions and synaptic deficits.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314159 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314159 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1390184 ncbi.nlm.nih.gov/bioproject/PRJNA1390184 ↗
project · from NCBI GEO
- PubMed 42446992 pubmed.ncbi.nlm.nih.gov/42446992 ↗
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 | GSE314159 | 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 |