Omics · study · 2026
Sex and life experience shape locus coeruleus pretangle tau pathology
Listed in NCBI GEO
The locus coeruleus (LC) is the earliest site of tau pathology in Alzheimer’s disease (AD), yet how modifiable environmental factors influence its vulnerability, particularly in a sex-specific manner, remains unclear.
Description
Using a rat model expressing pseudophosphorylated human tau (htauE14) in the LC, we show that tau accumulation induces anxiety-like behavior, cognitive deficits, and tau spread, shaped by sex and life history.
Early-life enrichment attenuated tau propagation, reduced neuroinflammation, and increased hippocampal BDNF expression, while late enrichment reduced anxiety and improved learning. In contrast, late-life stress exacerbated LC degeneration. Single-nucleus RNA sequencing revealed female-biased transcriptional dysregulation in hippocampal excitatory neurons and glia cells following htauE14 expression.
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Environmental exposures drove distinct cell type-specific transcriptomic signatures: early stress further disrupted mitochondrial and synaptic programs, whereas early enrichment conferred transcriptional stability. These findings position the LC as a sexually dimorphic and environmentally sensitive node of early AD vulnerability and highlight the preventive potential of early-life interventions.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE306nnn/GSE306235 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE306235 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1309729 ncbi.nlm.nih.gov/bioproject/PRJNA1309729 ↗
project · from NCBI GEO
- PubMed 41804725 pubmed.ncbi.nlm.nih.gov/41804725 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Rattus norvegicus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · RNA sequencing 75% · Sequencing 75%
Provenance · 1 source records, 10 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE306235 | 15 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:10116 | 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 |