Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers
Previous studies have shown activation of the immune system and altered immune response in Huntington's disease (HD) gene carriers. Here, we hypothesized that peripheral and central immune responses could be concurrent pathophysiological events and represent a global innate immune response to t...
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| Format: | Article |
| Language: | English |
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Elsevier
2015-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996115300322 |
| _version_ | 1818337312135708672 |
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| author | Marios Politis Nayana Lahiri Flavia Niccolini Paul Su Kit Wu Paolo Giannetti Rachael I. Scahill Federico E. Turkheimer Sarah J. Tabrizi Paola Piccini |
| author_facet | Marios Politis Nayana Lahiri Flavia Niccolini Paul Su Kit Wu Paolo Giannetti Rachael I. Scahill Federico E. Turkheimer Sarah J. Tabrizi Paola Piccini |
| author_sort | Marios Politis |
| collection | DOAJ |
| description | Previous studies have shown activation of the immune system and altered immune response in Huntington's disease (HD) gene carriers. Here, we hypothesized that peripheral and central immune responses could be concurrent pathophysiological events and represent a global innate immune response to the toxic effects of mutant huntingtin in HD gene carriers. We sought to investigate our hypothesis using [11C]PK11195 PET as a translocator protein (TSPO) marker of central microglial activation, together with assessment of peripheral plasma cytokine levels in a cohort of premanifest HD gene carriers who were more than a decade from predicted symptomatic conversion. Data were also compared to those from a group of healthy controls matched for age and gender. We found significantly increased peripheral plasma IL-1β levels in premanifest HD gene carriers compared to the group of normal controls (P = 0.018). Premanifest HD gene carriers had increased TSPO levels in cortical, basal ganglia and thalamic brain regions (P < 0.001). Increased microglial activation in somatosensory cortex correlated with higher plasma levels of IL-1β (rs = 0.87, P = 0.013), IL-6 (rs = 0.85, P = 0.013), IL-8 (rs = 0.68, P = 0.045) and TNF-α (rs = 0.79; P = 0.013). Our findings provide first in vivo evidence for an association between peripheral and central immune responses in premanifest HD gene carriers, and provide further supporting evidence for the role of immune dysfunction in the pathogenesis of HD. |
| first_indexed | 2024-12-13T14:53:13Z |
| format | Article |
| id | doaj.art-db7b12c187ca4b4c806a502eb4484aa6 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T14:53:13Z |
| publishDate | 2015-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-db7b12c187ca4b4c806a502eb4484aa62022-12-21T23:41:18ZengElsevierNeurobiology of Disease1095-953X2015-11-0183115121Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriersMarios Politis0Nayana Lahiri1Flavia Niccolini2Paul Su3Kit Wu4Paolo Giannetti5Rachael I. Scahill6Federico E. Turkheimer7Sarah J. Tabrizi8Paola Piccini9Neurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Brain Sciences, Department of Medicine, Imperial College London, London, UKHuntington's Disease Research Group, Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UKNeurodegeneration Imaging Group, Department of Basic and Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Division of Brain Sciences, Department of Medicine, Imperial College London, London, UKDivision of Brain Sciences, Department of Medicine, Imperial College London, London, UKDivision of Brain Sciences, Department of Medicine, Imperial College London, London, UKDivision of Brain Sciences, Department of Medicine, Imperial College London, London, UKHuntington's Disease Research Group, Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UKDepartment of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UKHuntington's Disease Research Group, Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, UKDivision of Brain Sciences, Department of Medicine, Imperial College London, London, UK; Corresponding author at: Division of Brian Sciences, Imperial College London, Hammersmith Hospital Campus, DuCane road, W12 0NN London, UK.Previous studies have shown activation of the immune system and altered immune response in Huntington's disease (HD) gene carriers. Here, we hypothesized that peripheral and central immune responses could be concurrent pathophysiological events and represent a global innate immune response to the toxic effects of mutant huntingtin in HD gene carriers. We sought to investigate our hypothesis using [11C]PK11195 PET as a translocator protein (TSPO) marker of central microglial activation, together with assessment of peripheral plasma cytokine levels in a cohort of premanifest HD gene carriers who were more than a decade from predicted symptomatic conversion. Data were also compared to those from a group of healthy controls matched for age and gender. We found significantly increased peripheral plasma IL-1β levels in premanifest HD gene carriers compared to the group of normal controls (P = 0.018). Premanifest HD gene carriers had increased TSPO levels in cortical, basal ganglia and thalamic brain regions (P < 0.001). Increased microglial activation in somatosensory cortex correlated with higher plasma levels of IL-1β (rs = 0.87, P = 0.013), IL-6 (rs = 0.85, P = 0.013), IL-8 (rs = 0.68, P = 0.045) and TNF-α (rs = 0.79; P = 0.013). Our findings provide first in vivo evidence for an association between peripheral and central immune responses in premanifest HD gene carriers, and provide further supporting evidence for the role of immune dysfunction in the pathogenesis of HD.http://www.sciencedirect.com/science/article/pii/S0969996115300322Huntington's diseaseMicrogliaPeripheral inflammationPETMRI |
| spellingShingle | Marios Politis Nayana Lahiri Flavia Niccolini Paul Su Kit Wu Paolo Giannetti Rachael I. Scahill Federico E. Turkheimer Sarah J. Tabrizi Paola Piccini Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers Neurobiology of Disease Huntington's disease Microglia Peripheral inflammation PET MRI |
| title | Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers |
| title_full | Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers |
| title_fullStr | Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers |
| title_full_unstemmed | Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers |
| title_short | Increased central microglial activation associated with peripheral cytokine levels in premanifest Huntington's disease gene carriers |
| title_sort | increased central microglial activation associated with peripheral cytokine levels in premanifest huntington s disease gene carriers |
| topic | Huntington's disease Microglia Peripheral inflammation PET MRI |
| url | http://www.sciencedirect.com/science/article/pii/S0969996115300322 |
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