Discriminating alpha-synuclein strains in Parkinson&#39;s disease and multiple system atrophy

doi:10.1038/s41586-020-1984-7

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-1984-7
	Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy
	Senior, Andrew W.1; Evans, Richard 1; Jumper, John 1; Kirkpatrick, James 1; Sifre, Laurent 1; Green, Tim 1; Qin, Chongli 1; Zidek, Augustin 1; Nelson, Alexander W. R.1; Bridgland, Alex 1; Penedones, Hugo 1; Petersen, Stig 1; Simonyan, Karen 1; Crossan, Steve 1; Kohli, Pushmeet 1; Jones, David T.2,3; Silver, David 1; Kavukcuoglu, Koray 1; Hassabis, Demis 1
	2020-01-30
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	578 期号:7794 页码:273-+
文章类型	Article
语种	英语
国家	USA; Sweden
英文关键词	Synucleinopathies are neurodegenerative diseases that are associated with the misfolding and aggregation of alpha-synuclein, including Parkinson' s disease, dementia with Lewy bodies and multiple system atrophy(1). Clinically, it is challenging to differentiate Parkinson' s disease and multiple system atrophy, especially at the early stages of disease(2). Aggregates of alpha-synuclein in distinct synucleinopathies have been proposed to represent different conformational strains of alpha-synuclein that can self-propagate and spread from cell to cell(3-6). Protein misfolding cyclic amplification (PMCA) is a technique that has previously been used to detect alpha-synuclein aggregates in samples of cerebrospinal fluid with high sensitivity and specificity(7,8). Here we show that the alpha-synuclein-PMCA assay can discriminate between samples of cerebrospinal fluid from patients diagnosed with Parkinson' s disease and samples from patients with multiple system atrophy, with an overall sensitivity of 95.4%. We used a combination of biochemical, biophysical and biological methods to analyse the product of alpha-synuclein-PMCA, and found that the characteristics of the alpha-synuclein aggregates in the cerebrospinal fluid could be used to readily distinguish between Parkinson' s disease and multiple system atrophy. We also found that the properties of aggregates that were amplified from the cerebrospinal fluid were similar to those of aggregates that were amplified from the brain. These findings suggest that alpha-synuclein aggregates that are associated with Parkinson' s disease and multiple system atrophy correspond to different conformational strains of alpha-synuclein, which can be amplified and detected by alpha-synuclein-PMCA. Our results may help to improve our understanding of the mechanism of alpha-synuclein misfolding and the structures of the aggregates that are implicated in different synucleinopathies, and may also enable the development of a biochemical assay to discriminate between Parkinson' s disease and multiple system atrophy. Protein misfolding cyclic amplification (PMCA) technology can discriminate between patients with Parkinson' s disease and patients with multiple system atrophy on the basis of the characteristics of the alpha-synuclein aggregates in the cerebrospinal fluid.
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000511285700005
WOS关键词	THIOPHENE-BASED LIGANDS ; OPTICAL LIGANDS ; PROTEIN ; DIAGNOSIS ; PLETHORA ; CSF
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281415
专题	地球科学资源环境科学气候变化
作者单位	1.DeepMind, London, England; 2.Francis Crick Inst, London, England; 3.UCL, London, England
推荐引用方式 GB/T 7714	Senior, Andrew W.,Evans, Richard,Jumper, John,et al. Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy[J]. NATURE,2020,578(7794):273-+.
APA	Senior, Andrew W..,Evans, Richard.,Jumper, John.,Kirkpatrick, James.,Sifre, Laurent.,...&Hassabis, Demis.(2020).Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy.NATURE,578(7794),273-+.
MLA	Senior, Andrew W.,et al."Discriminating alpha-synuclein strains in Parkinson's disease and multiple system atrophy".NATURE 578.7794(2020):273-+.