Association between alpha-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease

作者：Locascio Joseph J; Eberly Shirley; Liao Zhixiang; Liu Ganqiang; Hoesing Ashley N; Duong Karen; Trisini Lipsanopoulos Ana; Dhima Kaltra; Hung Albert Y; Flaherty Alice W; Schwarzschild Michael A; Hayes Michael T; Wills Anne Marie; Sohur U Shivraj; Mejia Nicte I; Selkoe Dennis J; Oakes David; Shoulson Ira; Dong Xianjun; Marek Ken; Zheng Bin; Ivinson Adrian; Hyman Bradley T; Growdon John H; Sudarsky Lewis R; Schlossmacher Michael G; Ravina Bernard

来源：Brain, 2015, 138(9): 2659-2671.

DOI：10.1093/brain/awv202

• alpha-synuclein
• biomarker
• gene expression
• biobank
• mitochondria
• cognitive decline

There are no cures for neurodegenerative diseases and this is partially due to the difficulty of monitoring pathogenic molecules in patients during life. The Parkinson's disease gene a-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circulating blood cells are paradoxically reduced in early stage, untreated and dopamine transporter neuroimaging-supported Parkinson's disease in three independent regional, national, and international populations representing 500 cases and 363 controls and on three analogue and digital platforms with P50.0001 in meta-analysis. Individuals with SNCA transcripts in the lowest quartile of counts had an odds ratio for Parkinson's disease of 2.45 compared to individuals in the highest quartile. Disease-relevant transcript isoforms were low even near disease onset. Importantly, low SNCA transcript abundance predicted cognitive decline in patients with Parkinson's disease during up to 5 years of longitudinal follow-up. This study reveals a consistent association of reduced SNCA transcripts in accessible peripheral blood and early-stage Parkinson's disease in 863 participants and suggests a clinical role as potential predictor of cognitive decline. Moreover, the three independent biobank cohorts provide a generally useful platform for rapidly validating any biological marker of this common disease.

• 出版日期2015-9-1