Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia
The IVS 10+16 MAPT mutation significantly disrupts cortical differentiation and synaptic maturation, evidenced by downregulated genes associated with synapses and neuronal development. Tau-mutant cortical organoids exhibit mitochondrial dysfunction, with fewer and smaller mitochondria alongside tau hyperphosphorylation and aggregation, which further contribute to neuronal damage and disease progression. Treatment with bezafibrate effectively normalizes mitochondrial parameters, enhances neuronal integrity and synaptic maturation, and restores network functionality, showcasing its promise as a therapeutic strategy for tauopathies. The 3D in vitro disease model used in this study proves valuable for studying tauopathies and testing new drugs, effectively mimicking key aspects of tau-related neurodegeneration.
Authors
- Federica Cordella (ORCID: https://orcid.org/0000-0001-8578-4489)
- Mara Cirone (ORCID: https://orcid.org/0000-0002-2207-9624)
- Silvia Ghirga (ORCID: https://orcid.org/0000-0002-7748-3704)
- Chiara D’Antoni (ORCID: https://orcid.org/0000-0001-8745-2410)
- Paola Bezzi (ORCID: https://orcid.org/0000-0002-8279-3600)
- Silvia Di Angelantonio (ORCID: https://orcid.org/0000-0003-1434-3648)
- Debora Salerno (ORCID: https://orcid.org/0000-0003-0504-1904)
- Lorenza Mautone (ORCID: https://orcid.org/0000-0002-0510-1420)
- Maria Anele Romeo (ORCID: https://orcid.org/0000-0002-6666-0103)
- Lucrezia Tondo (ORCID: https://orcid.org/0009-0004-9039-5452)
- Erika Parente (ORCID: https://orcid.org/0000-0003-1246-4876)
Institutions
- Italian Institute of Technology (IT)
- Donawa Lifescience Consulting (Italy) (IT)
- Center for Nano Science and Technology (IT)
- Sapienza University of Rome (IT)
- University of Lausanne (CH)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1002/alz.70419
- Citations
- 1
- Primary Topic
- Amino Acid Enzymes and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.11