Reduced erythrocytic CHCHD2 mRNA is associated with brain pathology of Parkinson’s disease

Acta Neuropathologica Communications

Genliang Liu¹  Tao Feng²  Zongran Liu³  Ying Yang³  Qilong Wang³  Xiaodan Liu⁴  Jing Zhang⁵  Tessandra Stewart⁶  Eric Thorland⁶  Eugene M. Cilento⁶  David Soltys⁶  Min Shi⁶  Yiran Hou⁷ 

[1] Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, 100070, Beijing, China;China National Clinical Research Center for Neurological Diseases, 100070, Beijing, China;Center for Movement Disorders, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, 100070, Beijing, China;China National Clinical Research Center for Neurological Diseases, 100070, Beijing, China;Parkinson’s Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, 100069, Beijing, China;Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, 100191, Beijing, China;Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, 100191, Beijing, China;Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, China;Department of Pathology, School of Basic Medical Sciences, Peking University Third Hospital, Peking University Health Science Center, 100191, Beijing, China;Department of Pathology, The First Affiliated Hospital and School of Medicine, Zhejiang University, Hangzhou, China;China National Health and Disease Human Brain Tissue Resource Center, Hangzhou, China;Department of Pathology, School of Medicine, University of Washington, Seattle, WA, USA;The Affiliated High School of Peking University, 100080, Beijing, China;

关键词: Parkinson’s disease;    Mitochondria dysfunction;    α-synuclein;    CHCHD2;   

DOI  :  10.1186/s40478-021-01133-6

来源: Springer

【 摘 要 】

Peripheral biomarkers indicative of brain pathology are critically needed for early detection of Parkinson’s disease (PD). In this study, using NanoString and digital PCR technologies, we began by screening for alterations in genes associated with PD or atypical Parkinsonism in erythrocytes of PD patients, in which PD-related changes have been reported, and which contain ~ 99% of blood α-synuclein. Erythrocytic CHCHD2 mRNA was significantly reduced even at the early stages of the disease. A significant reduction in protein and/or mRNA expression of CHCHD2 was confirmed in PD brains collected at autopsy as well as in the brains of a PD animal model overexpressing α-synuclein, in addition to seeing a reduction of CHCHD2 in erythrocytes of the same animals. Overexpression of α-synuclein in cellular models of PD also resulted in reduced CHCHD2, via mechanisms likely involving altered subcellular localization of p300 histone acetyltransferase. Finally, the utility of reduced CHCHD2 mRNA as a biomarker for detecting PD, including early-stage PD, was validated in a larger cohort of 205 PD patients and 135 normal controls, with a receiver operating characteristic analysis demonstrating > 80% sensitivity and specificity.

【 授权许可】

CC BY