Abstract
Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington’s disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30–40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from n = 125 subjects, including n = 37 manifest HD patients, n = 36 premanifest patients, and n = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.
Highlights
Huntington’s disease (HD) is an autosomal-dominant, progressive neurodegenerative disorder that is caused by a CAG-repeat expansion in the Huntington (HTT) gene [1]
It is clear that the pathology of HD is not exclusively restricted to the brain and several peripheral abnormalities are known to occur in HD patients, including weight loss, altered glucose homeostasis, skeletal muscle wasting and cellular abnormalities [4,5,6]
Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, play an important role in the pathophysiology associated with HD [7,8]
Summary
Huntington’s disease (HD) is an autosomal-dominant, progressive neurodegenerative disorder that is caused by a CAG-repeat expansion in the Huntington (HTT) gene [1]. Specific increases in proinflammatory cytokines, including interleukin 6 (IL-6), interleukin 8, and tumor necrosis factor alpha (TNF-a), have been found in the brains from HD patients and mouse models of HD [9,10,11,12]. Peripheral findings support these brain studies, in that several studies have demonstrated increases in IL-6, C-reactive protein (CRP), and transforming growth factor beta 1, in plasma from human HD patients when compared with controls [10,13,14,15]. Biomarkers reflecting these peripheral and/or central derangements of neuroinflammation could be useful to better characterize disease progression and the therapeutic response to specific interventions
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