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

Author:

Pan Lina1ORCID,Li Chunrui1,Meng Lanxia1,Tian Ye1,He Mingyang2,Yuan Xin1,Zhang Guoxin1ORCID,Zhang Zhaohui1,Xiong Jing13,Chen Guiqin1,Zhang Zhentao1ORCID

Affiliation:

1. Department of Neurology, Renmin Hospital of Wuhan University , Wuhan 430060 , China

2. Hubei Provincial Institute for Food Supervision and Test , Wuhan 430070 , China

3. Department of Pathology and Laboratory Medicine, Emory University School of Medicine , Atlanta, GA 30322 , USA

Abstract

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

Funder

National Key Basic Research Program of China

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Neurology (clinical)

Reference83 articles.

1. Diagnosis and treatment of Parkinson disease: A review;Armstrong;JAMA,2020

2. The clinical symptoms of Parkinson’s disease;Sveinbjornsdottir;J Neurochem,2016

3. Non-motor symptoms of Parkinson’s disease: Diagnosis and management;Chaudhuri;Lancet Neurol,2006

4. Parkinson disease;Balestrino;Eur J Neurol,2020

5. Cell biology and pathophysiology of α-synuclein;Burré;Cold Spring Harb Perspect Med,2018

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