Tau neurotoxicity without the lesions: a fly challenges a tangled web.

Models of neurodegenerative disorders are challenging the classical defining role of tangles in neurotoxicity. In flies, tau overexpression is sufficient to cause neuronal death without the formation of fibrillar aggregates. This parallels observations in models of polyglutamine disorders and suggests that aggregated protein might not be the toxic species responsible for neuronal dysfunction and cell death.