Application of α-Syn Real-Time Quaking-Induced Conversion for Brain and Skin Specimens of the Chinese Patients With Parkinson's Disease

Dong-Dong Chen; Ling Jiao; Yue Huang; Kang Xiao; Li-Ping Gao; Cao Chen; Qi Shi; Xiao-Ping Dong

doi:10.3389/fnagi.2022.898516

Application of α-Syn Real-Time Quaking-Induced Conversion for Brain and Skin Specimens of the Chinese Patients With Parkinson's Disease

Front Aging Neurosci. 2022 Jul 1:14:898516. doi: 10.3389/fnagi.2022.898516. eCollection 2022.

Authors

Dong-Dong Chen¹, Ling Jiao², Yue Huang³, Kang Xiao¹, Li-Ping Gao¹, Cao Chen^{1

4}, Qi Shi^{1

5}, Xiao-Ping Dong^{1

4

5

6}

Affiliations

¹ State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Zhejiang University, Beijing, China.
² Department of Neurology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
³ Department of Neurology, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
⁵ China Academy of Chinese Medical Sciences, Beijing, China.
⁶ Shanghai Institute of Infectious Disease and Biosafety, Shanghai, China.

Abstract

The real-time quaking-induced conversion (RT-QuIC) assay has been developed and used as an in vitro diagnostic tool for Parkinson's disease (PD). In this study, we established α-Syn RT-QuIC using recombinant human α-Syn as the substrate. All 5 brain homogenates of neuropathological PD cases and 13 skin homogenates of clinical PD cases showed positive results, whereas all the samples of negative controls remain negative. Meantime, randomly selected 6 skin samples of PD cases and 6 skin samples of sCJD cases showed negative in opposite prion RT-QuIC and α-Syn RT-QuIC. Our α-Syn RT-QuIC showed dose-dependent manner between the lag times and peak ThT fluorescent values. Additionally, the detecting limitation was about 10^-7 dilution for brain tissues and 10^-6 for skins. Those data indicate a reliable specificity and good sensitivity of the established α-Syn RT-QuIC in identifying and amplifying the misfolded α-Syn in brain and skin tissues of patients with PD.

Keywords: Parkinson’s disease (PD); PrPsc; RT-QuIC; prion disease (PrD); α-synuclein.