Tau accelerates α-synuclein aggregation and spreading in Parkinson's disease

The aggregation and prion-like propagation of alpha-synuclein are involved in the pathogenesis of Parkinson's disease. However, the underlying mechanisms regulating the assembly and spreading of alpha-synuclein fibrils remain poorly understood. Tau co-deposits with alpha-synuclein in the brains of Parkinson's disease patients, suggesting a pathological interplay between them. Here we show that tau interacts with alpha-synuclein and accelerates its aggregation. Compared with pure alpha-synuclein fibrils, the tau-modified alpha-synuclein fibrils show enhanced seeding activity, inducing mitochondrial dysfunction, synaptic impairment and neurotoxicity in vitro. Injection of the tau-modified alpha-synuclein fibrils into the striatum of mice induces more severe alpha-synuclein pathology, motor dysfunction and cognitive impairment when compared with the mice injected with pure alpha-synuclein fibrils. Knockout of tau attenuates the propagation of alpha-synuclein pathology and Parkinson's disease-like symptoms both in mice injected with alpha-syn fibrils and alpha-syn A53T transgenic mice. In conclusion, tau facilitates alpha-synuclein aggregation and propagation in Parkinson's disease. Tau deposits are common in the brains of patients with Parkinson's disease; however, the role of tau in the disorder remains unclear. Pan et al. demonstrate that tau binds alpha-synuclein and promotes its aggregation, contributing to the onset of Parkinson's disease.