Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer’s disease

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. Our findings identify a failed astrocyte stress response to amyloid-β as an early inducer of amyloid and tau co-morbidity, a noxious process in AD acting through a non-canonical secretase pathway.

Authors

Institutions

Publication Details

Journal
Nature Communications
Published
2025-10-31
DOI
https://doi.org/10.1038/s41467-025-65536-y
Citations
1
Primary Topic
Alzheimer's disease research and treatments
Type
article
Field-Weighted Citation Impact
1.16

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer’s disease

Vanessa Schmidt, Ewa Żurawska-Płaksej, Tomasz Obrębski, Anna R. Malik et al.
1 citations
Nature Communications
Alzheimer's disease research and treatments
1.16
article

Astrocytes distress triggers brain pathology through induction of δ secretase in a murine model of Alzheimer’s disease

Vanessa Schmidt, Ewa Żurawska-Płaksej, Tomasz Obrębski, Anna R. Malik, Thomas E. Willnow, Johan Palmfeldt, Jarosław Cendrowski, Ewelina Ziemlińska, Barbara L. Hempstead, Jemila P. Gomes
article en
1 citations

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. Our findings identify a failed astrocyte stress response to amyloid-β as an early inducer of amyloid and tau co-morbidity, a noxious process in AD acting through a non-canonical secretase pathway.

Nature CommunicationsVol. 16(1)
Helmholtz Association of German Research Centres (DE), Aarhus University (DK), Max Delbrück Center (DE), Cornell University (US), Wroclaw Medical University (PL), National Institute of Oncology (HU), International Institute of Molecular and Cell Biology (PL), University of Warsaw (PL)
Alzheimer Forschung Initiative, Novo Nordisk, Uniwersytet Warszawski, Novo Nordisk Fonden, Medical Research Council
Openalex Percentile: Top 16%
Alzheimer's disease research and treatments
1.16
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.