![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
6MB |
![[thumbnail of Supplementary Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Information)
15MB |
| Item Type: | Article |
|---|---|
| Title: | Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer’s disease |
| Creators Name: | Schmidt, Vanessa, Ziemlinska, Ewelina, Obrebski, Tomasz, Gomes, Jemila P., Zurawska-Plaksej, Ewa, Cendrowski, Jaroslaw, Palmfeldt, Johan, Hempstead, Barbara L., Willnow, Thomas E. and Malik, Anna R. |
| Abstract: | The importance of astrocytes for Alzheimer’s disease (AD) pathology is increasingly appreciated, yet the mechanisms whereby this cell type impacts neurodegenerative processes remain elusive. Here we show that, in a genetic mouse model with diminished astrocyte stress response, even low levels of amyloid-β trigger astrocyte reactivity, resulting in brain inflammation and massive amyloid and tau pathologies. This dysfunctional response of astrocytes to amyloid-β acts through activation of δ secretase, a stress-induced protease implicated in both amyloid and tau-related proteolytic processing. Ourfindingsidentify a failed astrocyte stress response to amyloid-βas an early inducer of amyloid and tau co-morbidity, a noxious process in AD acting through a non-canonical secretase pathway. |
| Keywords: | Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid Beta-Peptides, Animal Disease Models, Astrocytes, Brain, Inbred C57BL Mice, Transgenic Mice, Tau Proteins, Animals, Mice |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 9653 |
| Date: | 31 October 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-65536-y |
| PubMed: | View item in PubMed |
| Related to: |
Repository Staff Only: item control page
