| 1. |
- Björkqvist, Maria, et al.
(författare)
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A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
- 2008
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205, s. 1869-1877
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Björkqvist, Maria, et al.
(författare)
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Harnessing immune alterations in neurodegenerative diseases.
- 2009
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 64:1, s. 21-24
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Tidskriftsartikel (refereegranskat)abstract
- Immune dysfunction, a well-established feature of neuroinflammatory disease, is increasingly recognized in neurodegenerative conditions. Its role is emerging as an early and active participant in neuropathology. Inflammation could be modified, with disease-slowing effects, by targeted interventions; it is also readily detectable and could serve as a source of valuable biomarkers.
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| 3. |
- Dalrymple, Annette, et al.
(författare)
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Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates
- 2007
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:7, s. 2833-2840
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine and immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling to reveal plasma changes with HD progression. Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers.
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