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Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia
Federica Cordella, Lorenza Mautone, Debora Salerno, Lucrezia Tondo, Silvia Ghirga, Chiara D’Antoni, Erika Parente, Maria Anele Romeo et al.. Alzheimer s & Dementia, 2025-08-01
Topic: Brain proteins, microglia and lab models
Tau mutant cortical organoids showed altered mitochondrial function and gene expression related to neuronal development, with synaptic markers and neuronal activity reduction. Bezafibrate treatment restored mitochondrial content and rescued synaptic functionality and tau physiology. These findings suggest that targeting mitochondrial function with bezafibrate could potentially reverse tau-induced neurodevelopmental deficits, highlighting its therapeutic potential for tauopathies like frontotemporal dementia. HIGHLIGHTS: 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.
Key findings
- Tau mutant cortical organoids showed altered mitochondrial function and gene expression related to neuronal development, with synaptic markers and neuronal activity reduction.
- Bezafibrate treatment restored mitochondrial content and rescued synaptic functionality and tau physiology.
- These findings suggest that targeting mitochondrial function with bezafibrate could potentially reverse tau-induced neurodevelopmental deficits, highlighting its therapeutic potential for tauopathies like frontotemporal dementia.
- HIGHLIGHTS: 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.
Why it matters
In a 3D cortical organoid model of MAPT frontotemporal dementia, bezafibrate treatment restored mitochondrial content and rescued synaptic functionality and tau physiology. This is an in-vitro model, so it is early and preliminary and does not yet show a treatment for people.
Study details
- Evidence strengthLow
How this study scored 39/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer s & Dementia) |
| Journal's citation record | 2 / 4 | Alzheimer s & Dementia: journal h-index 228 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “organoid”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Silvia Di Angelantonio: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Sapienza University of Rome: institution h-index 1,145 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40810332) |
| Free to read | 2 / 2 | Free to read |
| Total | 39 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Cordella, F., Mautone, L., Salerno, D., Tondo, L., Ghirga, S., D’Antoni, C., et al. (2025). Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia. Alzheimer s & Dementia. https://doi.org/10.1002/alz.70419
Vancouver
Cordella F, Mautone L, Salerno D, Tondo L, Ghirga S, D’Antoni C, et al. Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia. Alzheimer s & Dementia. 2025. doi:10.1002/alz.70419. PMID: 40810332.
BibTeX
@article{cordella2025-40810332,
author = {Cordella, Federica and Mautone, Lorenza and Salerno, Debora and Tondo, Lucrezia and Ghirga, Silvia and D’Antoni, Chiara and Parente, Erika and Romeo, Maria Anele and others},
title = {{Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia}},
journal = {Alzheimer s \& Dementia},
year = {2025},
doi = {10.1002/alz.70419},
pmid = {40810332},
url = {https://doi.org/10.1002/alz.70419}
}
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