Garcia-Segura Monica Emili, Perez-Rodriguez Diego, Chambers Darren, Jaunmuktane Zane, Proukakis Christos
Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, University College London, London, UK.
The Dubowitz Neuromuscular Centre, Division of Neuropathology, UCL Queen Square Institute of Neurology, University College London, London, UK.
Mov Disord. 2023 Feb;38(2):338-342. doi: 10.1002/mds.29291. Epub 2022 Nov 30.
Somatic α-synuclein (SNCA) copy number variants (CNVs, specifically gains) occur in multiple system atrophy (MSA) and Parkinson's disease brains.
The aim was to compare somatic SNCA CNVs in MSA subtypes (striatonigral degeneration [SND] and olivopontocerebellar atrophy [OPCA]) and correlate with inclusions.
We combined fluorescent in situ hybridization with immunofluorescence for α-synuclein and in some cases oligodendrocyte marker tubulin polymerization promoting protein (TPPP).
We analyzed one to three brain regions from 24 MSA cases (13 SND, 11 OPCA). In a region preferentially affected in one subtype (putamen in SND, cerebellum in OPCA), mosaicism was higher in that subtype, and cells with CNVs were 4.2 times more likely to have inclusions. In the substantia nigra, nonpigmented cells with CNVs and TPPP were about six times more likely to have inclusions.
The correlation between SNCA CNVs and pathology (at a regional level) and inclusions (at a single-cell level) suggests a role for somatic SNCA CNVs in MSA pathogenesis. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
体细胞α-突触核蛋白（SNCA）拷贝数变异（CNV，特别是增加）出现在多系统萎缩（MSA）和帕金森病患者的大脑中。
比较多系统萎缩各亚型（纹状体黑质变性[SND]和橄榄脑桥小脑萎缩[OPCA]）中的体细胞SNCA拷贝数变异，并与包涵体进行关联分析。
我们将荧光原位杂交与α-突触核蛋白的免疫荧光相结合，在某些情况下还与少突胶质细胞标记物微管蛋白聚合促进蛋白（TPPP）相结合。
我们分析了24例多系统萎缩患者（13例纹状体黑质变性，11例橄榄脑桥小脑萎缩）的1至3个脑区。在一个亚型中优先受累的区域（纹状体黑质变性中的壳核，橄榄脑桥小脑萎缩中的小脑），该亚型中的镶嵌现象更高，并且具有拷贝数变异的细胞出现包涵体的可能性高4.2倍。在黑质中，具有拷贝数变异和TPPP的非色素细胞出现包涵体的可能性大约高6倍。
SNCA拷贝数变异与病理改变（在区域水平）和包涵体（在单细胞水平）之间的相关性表明体细胞SNCA拷贝数变异在多系统萎缩发病机制中起作用。© 2022作者。《运动障碍》由Wiley Periodicals LLC代表国际帕金森和运动障碍协会出版。
