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Plasma protein biomarkers of Alzheimer's disease endophenotypes in asymptomatic older twins: early cognitive decline and regional brain volumes.
Kiddle, S J; Steves, C J; Mehta, M; Simmons, A; Xu, X; Newhouse, S; Sattlecker, M; Ashton, N J; Bazenet, C; Killick, R; Adnan, J; Westman, E; Nelson, S; Soininen, H; Kloszewska, I; Mecocci, P; Tsolaki, M; Vellas, B; Curtis, C; Breen, G; Williams, S C R; Lovestone, S; Spector, T D; Dobson, R J B.
  • Kiddle SJ; MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Steves CJ; Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
  • Mehta M; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Simmons A; 1] Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Xu X; 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Newhouse S; 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Sattlecker M; 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Ashton NJ; 1] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK [2] Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Bazenet C; 1] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK [2] Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Killick R; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Adnan J; Department of Old Age Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Westman E; Department of Neurobiology, Care Sciences and Society, Karolinska Instituet, Stockholm, Sweden.
  • Nelson S; SomaLogic, Boulder, CO, USA.
  • Soininen H; 1] Institute of Clinical Medicine - Neurology, University of Eastern Finland, Kuopio, Finland [2] NeuroCenter, Kuopio University Hospital, Kuopio, Finland.
  • Kloszewska I; Department of Old Age Psychiatry and Psychotic disorders, Medical University of Lódz, Lódz, Poland.
  • Mecocci P; Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
  • Tsolaki M; 3rd Department of Neurology, Aristotle University, Thessaloniki, Greece.
  • Vellas B; Department of Internal Medicine and Geriatric Medicine, INSERM University of Toulouse, Toulouse, France.
  • Curtis C; 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Breen G; 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
  • Williams SC; Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
  • Lovestone S; Department of Psychiatry, Oxford University, Warneford Hospital, Oxford, UK.
  • Spector TD; Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
  • Dobson RJ; 1] MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK [2] NIHR Biomedical Research Centre for Mental Health and Biomedical Research Unit for Dementia at South London and Maudsley NHS Foundation, London, UK.
Transl Psychiatry ; 5: e584, 2015 Jun 16.
Article en En | MEDLINE | ID: mdl-26080319
ABSTRACT
There is great interest in blood-based markers of Alzheimer's disease (AD), especially in its pre-symptomatic stages. Therefore, we aimed to identify plasma proteins whose levels associate with potential markers of pre-symptomatic AD. We also aimed to characterise confounding by genetics and the effect of genetics on blood proteins in general. Panel-based proteomics was performed using SOMAscan on plasma samples from TwinsUK subjects who are asymptomatic for AD, measuring the level of 1129 proteins. Protein levels were compared with 10-year change in CANTAB-paired associates learning (PAL; n = 195), and regional brain volumes (n = 34). Replication of proteins associated with regional brain volumes was performed in 254 individuals from the AddNeuroMed cohort. Across all the proteins measured, genetic factors were found to explain ~26% of the variability in blood protein levels on average. The plasma level of the mitogen-activated protein kinase (MAPK) MAPKAPK5 protein was found to positively associate with the 10-year change in CANTAB-PAL in both the individual and twin difference context. The plasma level of protein MAP2K4 was found to suggestively associate negatively (Q < 0.1) with the volume of the left entorhinal cortex. Future studies will be needed to assess the specificity of MAPKAPK5 and MAP2K4 to eventual conversion to AD.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Gemelos / Encéfalo / Proteínas Serina-Treonina Quinasas / MAP Quinasa Quinasa 4 / Péptidos y Proteínas de Señalización Intracelular / Endofenotipos / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2015 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Gemelos / Encéfalo / Proteínas Serina-Treonina Quinasas / MAP Quinasa Quinasa 4 / Péptidos y Proteínas de Señalización Intracelular / Endofenotipos / Enfermedad de Alzheimer Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Año: 2015 Tipo del documento: Article