Plasma inflammatory biomarkers for Huntington’s disease patients and mouse model

• Published in: Brain, behavior, and immunity Vol. 44; pp. 121 - 127
• Main Authors: Chang, Kuo-Hsuan, Wu, Yih-Ru, Chen, Yi-Chun, Chen, Chiung-Mei
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2015
• Subjects: Adult; Age Factors; Allergy and Immunology; Animals; Biomarker; Biomarkers - blood; Disease Models, Animal; Female; Humans; Huntington Disease - blood; Huntington Disease - complications; Huntington Disease - diagnosis; Huntington’s disease; Inflammation; Inflammation - blood; Inflammation - complications; Interleukin-18 - blood; Interleukin-6 - blood; Male; Matrix Metalloproteinase 9 - blood; Mice; Microglia - metabolism; Middle Aged; Motor Activity; Psychiatry; Transforming Growth Factor beta1 - blood; Vascular Endothelial Growth Factor A - blood; Biomarker; Huntington’s disease; Inflammation
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2014.09.011

•Increased plasma IL-6, MMP-9, VEGF, and TGF-β1 in HD patients.•Decreased IL-18 plasma levels in HD patients.•Plasma IL-6 reversely correlates with independence scale and functional capacity.•Alterations of the inflammatory markers were found in R6/2 mice at different ages.•These inflammatory markers may serve as the potential biomarkers for HD. Huntington’s disease (HD), caused by expanded CAG repeats encoding a polyglutamine tract in the huntingtin (HTT) protein, presents with a predominant degeneration of neurons in the striatum and cortex. Lines of evidence have observed neuroinflammation, particularly microglial activation, is involved in the pathogenesis of HD. Given that HTT is also expressed in peripheral inflammatory cells, it is possible that inflammatory changes detected in peripheral plasma may be biologically relevant and parallel the neuroinflammatory process of HD patients. By examining the expression levels of 13 microglia-derived inflammatory markers in the plasma of 5 PreHD carriers, 15 HD patients and 16 healthy controls, we found plasma levels of IL-6, MMP-9, VEGF and TGF-β1 were significantly increased in HD patients when compared with the controls, while plasma level of IL-18 were significantly reduced in HD patients compared with controls. Plasma level of IL-6 was reversely correlated with the UHDRS independence scale and functional capacity. To understand the temporal correlation between these inflammatory markers and HD progression, their levels were further tested in plasma from R6/2 mouse HD model at different ages. In rotarod test, R6/2 HD mice started to manifest HD phenotype at 7.5weeks of age. Higher plasma VEGF levels of R6/2 mice than those of age-matched wild-type (WT) littermates were noted from 7 (presymptomatic stage) to 13weeks of age (late symptomatic stage). The plasma IL-6 levels of R6/2 mice were higher than those of the WT littermates from 9 (early symptomatic stage) to 13weeks of age. R6/2 mice demonstrated higher MMP-9 and TGF-β1 levels than their WT littermates from 11 (middle symptomatic stage) to 13weeks of age. In contrast, the plasma IL-18 level was lower than those in WT littermates since 11weeks of age. These altered expressions of inflammatory markers may serve as the potential biomarkers for HD onset and progression. Specific inhibition/activation of these inflammatory markers may be the targets of HD drug development.