Discussion

Tauopathies encompass a wide range of neurodegenerative diseases and are characterized by aggregation and hyperphosphorylation of the microtubule-associated protein TAU. To develop a cure, there has been an increased focus on aggregation-prone proteins, and on the role of non-neuronal cell populations such as microglia and astrocytes. However, no disease-modifying therapy has been found to date.
Human iPSCs have the potential to accelerate therapeutic development, as they recapitulate disease-linked phenotypes while providing a human biological context. Ncardia has recently developed a human iPSC-derived Alzheimer’s disease model, using insoluble fractions of brain homogenates to mimic Alzheimer’s disease etiology as closely as possible.
The model’s relevance was confirmed through an evaluation of the presence of phenotypes associated to neurodegeneration and AD in high-throughput formats, using high-content imaging: TAU aggregation, lysosomal dysfunction and neuronal loss. Based on this data, the model was found to be applicable for use in discovery or preclinical in vitro testing of new therapeutic modalities.