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Genetic influence of plasma homocysteine on Alzheimer's disease.
Roostaei, Tina; Felsky, Daniel; Nazeri, Arash; De Jager, Philip L; Schneider, Julie A; Bennett, David A; Voineskos, Aristotle N.
Afiliación
  • Roostaei T; Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Cell Circuits Program, Broad
  • Felsky D; Cell Circuits Program, Broad Institute, Cambridge, MA, USA; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • Nazeri A; Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Mallinckrodt Institute of Ra
  • De Jager PL; Cell Circuits Program, Broad Institute, Cambridge, MA, USA; Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • Schneider JA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA; Department of Pathology, Rush University Medical Center, Chicago, IL, USA.
  • Bennett DA; Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
  • Voineskos AN; Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Underserved Populations Prog
Neurobiol Aging ; 62: 243.e7-243.e14, 2018 02.
Article en En | MEDLINE | ID: mdl-29102475
Observational studies have consistently reported elevated plasma homocysteine as a risk factor for Alzheimer's disease (AD). However, results from clinical trials of homocysteine-lowering treatments are inconsistent. This discrepancy may be explained by a lack of causal association between homocysteine and AD. Mendelian randomization studies have the potential to provide insight into the causality of this association through studying the effect of genetic predisposition to high homocysteine on AD. Our analyses using summarized (n = 54,162) and individual participant (n = 6987) data from Caucasian participants did not show an effect of plasma homocysteine genetic risk on susceptibility to AD. Although with smaller sample sizes, further subanalyses also did not support an effect of genetically determined plasma homocysteine on cognitive impairment and decline, beta-amyloid and tau pathology and gray matter atrophy in AD. However, we found associations with tau tangle burden (n = 251) and gray matter atrophy (n = 605) in cognitively normal elderly. Our results do not support a causal association between elevated homocysteine and risk, severity, and progression of AD. However, the relationship between genetically determined homocysteine and brain pathology in cognitively normal elderly requires further exploration.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Estudios de Asociación Genética / Enfermedad de Alzheimer / Homocisteína Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Neurobiol Aging Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Predisposición Genética a la Enfermedad / Estudios de Asociación Genética / Enfermedad de Alzheimer / Homocisteína Tipo de estudio: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: Neurobiol Aging Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos