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GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer's disease implicates microglial activation gene IL1RAP.
Ramanan, Vijay K; Risacher, Shannon L; Nho, Kwangsik; Kim, Sungeun; Shen, Li; McDonald, Brenna C; Yoder, Karmen K; Hutchins, Gary D; West, John D; Tallman, Eileen F; Gao, Sujuan; Foroud, Tatiana M; Farlow, Martin R; De Jager, Philip L; Bennett, David A; Aisen, Paul S; Petersen, Ronald C; Jack, Clifford R; Toga, Arthur W; Green, Robert C; Jagust, William J; Weiner, Michael W; Saykin, Andrew J.
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  • Ramanan VK; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 1 Centre for Neuroim
  • Risacher SL; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Nho K; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA 5 Centre for Computational Biology and Bioinformatics, In
  • Kim S; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA 5 Centre for Computational Biology and Bioinformatics, In
  • Shen L; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA 5 Centre for Computational Biology and Bioinformatics, In
  • McDonald BC; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA 6 Department of Neurology, Indiana University School of M
  • Yoder KK; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Hutchins GD; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • West JD; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Tallman EF; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Gao S; 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA 7 Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • Foroud TM; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer
  • Farlow MR; 4 Indiana Alzheimer Disease Centre, Indiana University School of Medicine, Indianapolis, IN 46202, USA 6 Department of Neurology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • De Jager PL; 8 Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Brigham and Women's Hospital, Boston, MA 02115, USA 9 Departments of Neurology and Psychiatry, Harvard Medical School, Boston, MA 02115, USA 10 Program in Medical and Population Genetics, Broad Institute, Cambridg
  • Bennett DA; 11 Rush Alzheimer's Disease Centre, Rush University Medical Centre, Chicago, IL 60612, USA.
  • Aisen PS; 12 University of Southern California Alzheimer's Therapeutic Research Institute, San Diego, CA 92121, USA.
  • Petersen RC; 13 Department of Neurology, Mayo Clinic Minnesota, Rochester, MN 55905, USA.
  • Jack CR; 14 Department of Radiology, Mayo Clinic Minnesota, Rochester, MN 55905, USA.
  • Toga AW; 15 Laboratory of NeuroImaging, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
  • Green RC; 16 Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Jagust WJ; 17 Department of Neurology, University of California, Berkeley, CA 94720, USA.
  • Weiner MW; 18 Departments of Radiology, Medicine, and Psychiatry, University of California-San Francisco, San Francisco, CA 94143, USA 19 Department of Veterans Affairs Medical Centre, San Francisco, CA 94121, USA.
  • Saykin AJ; 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 1 Centre for Neuroimaging, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA 4 Indiana Alzheimer
Brain ; 138(Pt 10): 3076-88, 2015 Oct.
Article en En | MEDLINE | ID: mdl-26268530
ABSTRACT
Brain amyloid deposition is thought to be a seminal event in Alzheimer's disease. To identify genes influencing Alzheimer's disease pathogenesis, we performed a genome-wide association study of longitudinal change in brain amyloid burden measured by (18)F-florbetapir PET. A novel association with higher rates of amyloid accumulation independent from APOE (apolipoprotein E) ε4 status was identified in IL1RAP (interleukin-1 receptor accessory protein; rs12053868-G; P = 1.38 × 10(-9)) and was validated by deep sequencing. IL1RAP rs12053868-G carriers were more likely to progress from mild cognitive impairment to Alzheimer's disease and exhibited greater longitudinal temporal cortex atrophy on MRI. In independent cohorts rs12053868-G was associated with accelerated cognitive decline and lower cortical (11)C-PBR28 PET signal, a marker of microglial activation. These results suggest a crucial role of activated microglia in limiting amyloid accumulation and nominate the IL-1/IL1RAP pathway as a potential target for modulating this process.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Corteza Cerebral / Polimorfismo de Nucleótido Simple / Proteína Accesoria del Receptor de Interleucina-1 / Enfermedad de Alzheimer / Amiloide Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Brain Año: 2015 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Corteza Cerebral / Polimorfismo de Nucleótido Simple / Proteína Accesoria del Receptor de Interleucina-1 / Enfermedad de Alzheimer / Amiloide Tipo de estudio: Observational_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Brain Año: 2015 Tipo del documento: Article