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BRAIN Publication-derived

Bezafibrate treatment rescues neurodevelopmental and neurodegenerative defects in 3D cortical organoid model of MAPT frontotemporal dementia

Source Cordella et al., 2025 · Sapienza University of Rome · 10.1002/alz.70419

👤 Federica Cordella, Lorenza Mautone, Debora Salerno, Lucrezia Tondo, Silvia Ghirga, Chiara D'Antoni, Erika Parente, Maria Anele Romeo, Mara Cirone, Paola Bezzi, Silvia Di Angelantonio ⏱ 100 days 📋 4 phases 🧫 Human iPSC

Abstract

This protocol generates patterned 3D cortical organoids from isogenic control and MAPT IVS10+16 mutant human iPSC lines to model frontotemporal dementia. The protocol combines neural induction, neural differentiation, and terminal maturation over 100 days, with optional bezafibrate treatment to assess mitochondrial function and tau-related pathology rescue.

Cell source
Human iPSC
Application
Disease modeling

Protocol overview

12 steps across 4 phases

iPSC Maintenance and Cortical Organoid Initiation D0–D8
  1. 1 iPSC Culture Maintenance
  2. 2 iPSC Dissociation and Seeding into AggreWell800
  3. 3 Neural Induction Medium (NIM) Initiation
  4. 4 Daily Medium Changes During Neural Induction (D1–D8)
  5. 5 Organoid Harvest at D8
Neural Differentiation and Maturation D8–D30
  1. 1 Neural Differentiation Medium (NDM) Supplementation (D8–D30)
  2. 2 Transition to Neuronal Maturation Factors at D30
  3. 3 Medium Composition Change at D50
Late Maturation and Bezafibrate Treatment (Optional) D50–D100
  1. 1 Maintain Culture through D100
  2. 2 Bezafibrate (BZ) Treatment (D70–D100, Optional)
Organoid Dissociation to 2D Cortical Cultures (Optional) D70
  1. 1 Harvest and Dissociate Organoids
  2. 2 Plate Neurons onto Coated Dishes

Full SOP

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Attribution

This SOP was authored by Organthis based on the published method in Cordella et al., 2025. The originating laboratory holds no rights in this SOP and has not endorsed it unless marked Verified.

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