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A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
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- Björkqvist, Maria (author)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
- Wild, Edward J (author)
- Thiele, Jenny (author)
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- Silvestroni, Aurelio (author)
- Andre, Ralph (author)
- Lahiri, Nayana (author)
- Raibon, Elsa (author)
- Lee, Richard V (author)
- Benn, Caroline L (author)
- Woodman, Ben (author)
- Landles, Christian (author)
- Pouladi, Mahmoud A (author)
- Hayden, Michael R (author)
- Khalili-Shirazi, Azadeh (author)
- Lowdell, Mark W (author)
- Bates, Gillian P (author)
- Leavitt, Blair R (author)
- Möller, Thomas (author)
- Tabrizi, Sarah J (author)
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- (creator_code:org_t)
- 2008-07-14
- 2008
- English.
- In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205, s. 1869-1877
- Journal article (peer-reviewed)
Abstract
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- Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
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- Raibon, Elsa
- Lee, Richard V
- Benn, Caroline L
- Soulet, Denis
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- Landles, Christi ...
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- Hayden, Michael ...
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- Lowdell, Mark W
- Brundin, Patrik
- Bates, Gillian P
- Leavitt, Blair R
- Möller, Thomas
- Tabrizi, Sarah J
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