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Neural progenitor cells attenuate inflammatory reactivity and neuronal loss in an animal model of inflamed AD brain |
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| Authors: | Jae K Ryu Taesup Cho Yu Tian Wang James G McLarnon |
| Affiliation: | 1. Neurology Service and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Marqués de Valdecilla University Hospital (University of Cantabria), 39008, Santander, Spain 2. Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands 3. The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK 4. School of Molecular Medical Sciences, Institute of Genetics, University of Nottingham, Queens Medical Centre, Nottingham, NG7 2UH, UK 5. Centre for Paediatric Epidemiology and Biostatistics, Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK 6. Oxford Project to Investigate Memory and Ageing (OPTIMA), University Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford, OX1 3QX, UK 7. Department of Neurology, Erasmus MC University Medical Center, Rotterdam, the Netherlands 8. Department of Psychiatry, University of Bonn, Bonn, Germany 9. Department of Psychiatry, Derby City General Hospital, Uttoxeter Road, Derby, DE22 3NE, UK 10. Nuffield Department of Medicine, University of Oxford, Level 4, John Radcliffe Hospital, Oxford, OX3 9DU, UK 11. Dementia Research Group, Institute of Clinical Neurosciences, University of Bristol, Frenchay Hospital, Frenchay, Bristol, BS32 8BE, UK 12. Genética Molecular, Hospital Central de Asturias, Oviedo, Spain |
| Abstract: | BackgroundChronic inflammation is a characteristic of Alzheimer's disease (AD). An interaction associated with the risk of AD has been reported between polymorphisms in the regulatory regions of the genes for the pro-inflammatory cytokine, interleukin-6 (IL-6, gene: IL6), and the anti-inflammatory cytokine, interleukin-10 (IL-10, gene: IL10).MethodsWe examined this interaction in the Epistasis Project, a collaboration of 7 AD research groups, contributing DNA samples from 1,757 cases of AD and 6,295 controls.ResultsWe replicated the interaction. For IL6 rs2069837 AA × IL10 rs1800871 CC, the synergy factor (SF) was 1.63 (95% confidence interval: 1.10–2.41, p = 0.01), controlling for centre, age, gender and apolipoprotein E ε4 (APOEε4) genotype. Our results are consistent between North Europe (SF = 1.7, p = 0.03) and North Spain (SF = 2.0, p = 0.09). Further replication may require a meta-analysis. However, association due to linkage disequilibrium with other polymorphisms in the regulatory regions of these genes cannot be excluded.ConclusionWe suggest that dysregulation of both IL-6 and IL-10 in some elderly people, due in part to genetic variations in the two genes, contributes to the development of AD. Thus, inflammation facilitates the onset of sporadic AD. |
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