| First Author | Schmidt V | Year | 2025 |
| Journal | Nat Commun | Volume | 16 |
| Issue | 1 | Pages | 9653 |
| PubMed ID | 41173884 | Mgi Jnum | J:375490 |
| Mgi Id | MGI:8260284 | Doi | 10.1038/s41467-025-65536-y |
| Citation | Schmidt V, et al. (2025) Astrocytes distress triggers brain pathology through induction of delta secretase in a murine model of Alzheimer's disease. Nat Commun 16(1):9653 |
| abstractText | 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-beta trigger astrocyte reactivity, resulting in brain inflammation and massive amyloid and tau pathologies. This dysfunctional response of astrocytes to amyloid-beta acts through activation of delta secretase, a stress-induced protease implicated in both amyloid and tau-related proteolytic processing. Our findings identify a failed astrocyte stress response to amyloid-beta as an early inducer of amyloid and tau co-morbidity, a noxious process in AD acting through a non-canonical secretase pathway. |
