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Association between α-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease.
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; Zheng, Bin; Ivinson, Adrian; Hyman, Bradley T; Growdon, John H; Sudarsky, Lewis R; Schlossmacher, Michael G; Ravina, Bernard; Scherzer, Clemens R.
Afiliación
  • Locascio JJ; 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.
  • Eberly S; 3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • Liao Z; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Liu G; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Hoesing AN; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Bos
  • Duong K; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Bos
  • Trisini-Lipsanopoulos A; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Bos
  • Dhima K; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Bos
  • Hung AY; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Flaherty AW; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 6 Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Schwarzschild MA; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Hayes MT; 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Wills AM; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.
  • Shivraj Sohur U; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Mejia NI; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Selkoe DJ; 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Oakes D; 3 Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
  • Shoulson I; 8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007, USA.
  • Dong X; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Marek K; 8 Program for Regulatory Science and Medicine, Department of Neurology, Georgetown University, Washington, DC 20007, USA.
  • Zheng B; 1 Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical School and Brigham and Women's Hospital, Cambridge, MA 02139, USA 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Ivinson A; 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.
  • Hyman BT; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA 5 Biomarkers Program, Harvard NeuroDiscovery Center, Boston, MA 02115, USA.
  • Growdon JH; 2 Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Sudarsky LR; 7 Department of Neurology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Schlossmacher MG; 9 Institute for Neurodegenerative Disorders, New Haven, CT 06510, USA.
  • Ravina B; 10 Program in Neuroscience, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario K1H8M5, Canada.
  • Scherzer CR; 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 4 Ann Romney Centre for Neurologic Diseases, Brigham and Women's Hospita
Brain ; 138(Pt 9): 2659-71, 2015 Sep.
Article en En | MEDLINE | ID: mdl-26220939
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Alfa-Sinucleína Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Brain Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Alfa-Sinucleína Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Brain Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos