Astrocytes, via RTP801, contribute to cognitive decline by disrupting GABAergic‐regulated connectivity and driving neuroinflammation in an Alzheimer's disease mouse model
The 5xFAD mouse model of Alzheimer's disease presents higher levels of RTP801 in hippocampal astrocytes. Normalizing the levels of astrocytic RTP801 prevents cognitive decline and restores anxiety-like behavior in the 5xFAD mouse model. Knocking down astrocytic RTP801 preserves the resting-state functional connectivity in the 5xFAD mouse model. Astrocytic RTP801 mediates the loss of Parvalbumin+ interneurons, negatively affecting the levels of γ-aminobutyric acid (GABA) in the 5xFAD mouse model. Astrocytic RTP801 contributes to astro- and microgliosis and inflammasome expression in the 5xFAD mouse model.
Authors
- Albert Giralt (ORCID: https://orcid.org/0000-0001-5334-0963)
- Almudena Chicote‐González (ORCID: https://orcid.org/0009-0009-5459-1065)
- Jordi Alberch (ORCID: https://orcid.org/0000-0002-8684-2721)
- Esther Pérez‐Navarro (ORCID: https://orcid.org/0000-0001-9165-6539)
- Cristina Malagelada (ORCID: https://orcid.org/0000-0001-7185-436X)
- Pol Garcia‐Segura (ORCID: https://orcid.org/0000-0002-0169-824X)
- Júlia Solana‐Balaguer (ORCID: https://orcid.org/0000-0002-2263-0092)
- Genís Campoy‐Campos (ORCID: https://orcid.org/0000-0002-4235-7628)
- Manuel J. Rodrı́guez (ORCID: https://orcid.org/0000-0002-4476-004X)
- Ignacio Sánchez Pérez (ORCID: https://orcid.org/0000-0002-4367-0288)
- Guadalupe Sòria (ORCID: https://orcid.org/0000-0002-8344-0479)
Institutions
- Biomedical Research Networking Center on Neurodegenerative Diseases (ES)
- Departament de Salut (ES)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1002/alz.70051
- Citations
- 5
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 5.82
Funders
- Michael J. Fox Foundation for Parkinson's Research
- Fundación Ramón Areces
- Generalitat de Catalunya
- Ministerio de Ciencia e Innovación
- Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina
- Universitat de Barcelona
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación