Assessing the toxicity of tau aggregation.

Abnormally phosphorylated and aggregated tau protein is the primary component of pathological structures that are closely associated with neurodegeneration in Alzheimer's disease, Pick disease, corticobasal degeneration, progressive supranuclear palsy and many other neurodegenerative tauopathies, leading to the hypothesis that these structures are toxic mediators of disease progression. Results from animal models designed to test this hypothesis have yielded evidence that can suggest either a pathogenic, beneficial, or incidental role for tau aggregation. This review summarizes the differences in construction of recent model systems and assay methods that examine tau pathology and toxicity. We have found that the expression levels of tau and the modifications of tau used to enhance its aggregation have a large impact on the results. It is clear from the data that tau aggregation is toxic, but it is less clear which form of tau aggregate is the toxic species.