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APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study.
Ramanan, V K; Risacher, S L; Nho, K; Kim, S; Swaminathan, S; Shen, L; Foroud, T M; Hakonarson, H; Huentelman, M J; Aisen, P S; Petersen, R C; Green, R C; Jack, C R; Koeppe, R A; Jagust, W J; Weiner, M W; Saykin, A J.
Afiliação
  • Ramanan VK; 1] Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA [3] Medical Sci
  • Risacher SL; Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Nho K; Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Kim S; 1] Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA [2] Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Swaminathan S; 1] Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Shen L; 1] Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA [2] Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA.
  • Foroud TM; 1] Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA [3] Center for
  • Hakonarson H; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Huentelman MJ; The Translational Genomics Institute (TGen), Phoenix, AZ, USA.
  • Aisen PS; Department of Neuroscience, University of California, San Diego, CA, USA.
  • Petersen RC; Department of Neurology, Mayo Clinic Minnesota, Rochester, MN, USA.
  • Green RC; Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
  • Jack CR; Department of Radiology, Mayo Clinic Minnesota, Rochester, MN, USA.
  • Koeppe RA; Department of Radiology, University of Michigan, Ann Arbor, MI, USA.
  • Jagust WJ; Department of Neurology, University of California, Berkeley, CA, USA.
  • Weiner MW; 1] Departments of Radiology, Medicine, and Psychiatry, University of California, San Francisco, CA, USA [2] Department of Veterans Affairs Medical Center, San Francisco, CA, USA.
  • Saykin AJ; 1] Center for Neuroimaging, Department of Radiology and Imaging Sciences and Indiana Alzheimer's Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA [2] Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA [3] Center for
Mol Psychiatry ; 19(3): 351-7, 2014 Mar.
Article em En | MEDLINE | ID: mdl-23419831
Deposition of amyloid-ß (Aß) in the cerebral cortex is thought to be a pivotal event in Alzheimer's disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Aß load until now. We employed florbetapir ((18)F) positron emission tomography (PET) imaging to assess brain Aß levels in vivo for 555 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Aß load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within APOE (apolipoprotein E) (rs429358, P=5.5 × 10(-14)) and on chromosome 3 upstream of BCHE (butyrylcholinesterase) (rs509208, P=2.7 × 10(-8)) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Aß levels in this sample (APOE 10.7%, BCHE 4.3%). Suggestive associations were identified within ITGA6, near EFNA5, EDIL3, ITGA1, PIK3R1, NFIB and ARID1B, and between NUAK1 and C12orf75. These results confirm the association of APOE with Aß deposition and represent the largest known effect of BCHE on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the BCHE locus with Aß burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Butirilcolinesterase / Córtex Cerebral / Placa Amiloide / Doença de Alzheimer Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Butirilcolinesterase / Córtex Cerebral / Placa Amiloide / Doença de Alzheimer Idioma: En Ano de publicação: 2014 Tipo de documento: Article