Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.
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 α-synuclein (SNCA) is selectively expressed in blood cells and neurons. Here we show that SNCA transcripts in circula...
| Publicado en: | Brain: A Journal of Neurology Vol. 138; no. 9; pp. 2659 - 2672 |
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| Autores principales: | , , , , , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Oxford University Press / USA
Sep2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110531188&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110531188 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00068950 2RY jtl: Brain: A Journal of Neurology issn: 00068950 maglogo: N pubinfo: dt: Sep2015 vid: 138 iid: 9 pid: 622 pub: Oxford University Press / USA artinfo: ui: 110531188 NLM26220939 109546171 10.1093/brain/awv202 NLM26220939 PMC4643625 110531188 ppf: 2659 ppct: 13 formats: tig: atl: Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease. aug: au: 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 Shivraj Sohur, U Mejia, Nicte I Selkoe, Dennis J Oakes, David Shoulson, Ira Dong, Xianjun Marek, Ken affil: 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA sug: subj: Parkinson Disease Pathology Parkinson Disease Nerve Tissue Proteins Nerve Tissue Proteins Blood Genes Neuroradiography Aged Middle Age Male Parkinson Disease Radiography Cognition Disorders Severity of Illness Indices Microarray Analysis Cognition Disorders Etiology Female Genetic Screening Parkinson Disease Complications Alkaloids Diagnostic Use RNA Metabolism Dopamine Plasma Membrane Transport Proteins Metabolism Scales Funding Source Human Aged: 65+ years Middle Aged: 45-64 years Male Female ab: 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 α-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 P < 0.0001 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. pubtype: Academic Journal doctype: research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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