Disease modelling of frontotemporal dementia (FTD) in cerebral organoids

Title Disease modelling of frontotemporal dementia (FTD) in cerebral organoids
Acronym FTD-Organoids
Start date 2020-04-01
End date 2022-03-31
Sponsor Marie Skłodowska-Curie Action (MSCA)
Institution Institute of Molecular Biotechnology

Associated cell lines

Project Description

Frontotemporal dementia (FTD) is the second most common form of presenile dementia. Patients suffer from the degeneration of the frontal and temporal lobes leading typically to behavioral changes and language deficits. A pathological hallmark is the appearance of inclusion bodies that mainly consist of aggregated Tau, TDP-43 or FUS. It has been suggested that their prion-like spreading through the brain and the aberrant phase transition of stress granules are primary drivers of disease pathology. However, the exact molecular mechanisms and pathological consequences of these processes remain largely unknown. The goal of this project is to model FTD in human brain organoid cultures and determine if key pathological aspects that are observed in patients can be recapitulated. We will specifically study the propagation of pathological protein conformations and its effect on stress granule dynamics in a human cerebral organoids.