6 research outputs found
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Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington's Patients.
Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology
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Salivary Huntingtin in Huntington’s Disease
Huntington’s disease (HD), is an autosomal dominant disorder caused by an expansion of the CAG sequence in the huntingtin gene, which encodes the ubiquitously expressed Huntingtin (Htt) protein. Diminished motor function, cognition, and functional capacity are common symptoms. HD affects 10 in every 100,000 individuals in the US, with symptoms showing substantial variability in age at onset, severity and course of illness; thus warranting the need for reliable biomarkers to anticipate the onset of the disease and track its progression. The protein associated with the disease, huntingtin (Htt), is released into the extracellular fluid as neurodegeneration occurs in HD, and is thus a potentially useful biomarker. It has been previously measured in CSF and blood plasma in HD; however, these are invasive techniques with varying yields. We therefore wondered if Htt protein could be reliably measured in saliva. We assayed 98 saliva samples from manifest(HD), premanifest(PM), and age-matched normal control(NC) participants and found that salivary total Htt (tHtt) was significantly increased in HD saliva compared to NC. Salivary tHtt showed no gender effects and was significantly positively correlated with age in HD. As expected, tHtt levels had a positive correlation with motor symptoms and a negative correlation with cognitive ability and functional capacity in HD. Thus, tHtt protein can be reliably measured in human saliva and shows promise as a non-invasive clinically meaningful biomarker of disease progression in HD
Salivary Huntingtin in Huntington’s Disease
Huntington’s disease (HD), is an autosomal dominant disorder caused by an expansion of the CAG sequence in the huntingtin gene, which encodes the ubiquitously expressed Huntingtin (Htt) protein. Diminished motor function, cognition, and functional capacity are common symptoms. HD affects 10 in every 100,000 individuals in the US, with symptoms showing substantial variability in age at onset, severity and course of illness; thus warranting the need for reliable biomarkers to anticipate the onset of the disease and track its progression. The protein associated with the disease, huntingtin (Htt), is released into the extracellular fluid as neurodegeneration occurs in HD, and is thus a potentially useful biomarker. It has been previously measured in CSF and blood plasma in HD; however, these are invasive techniques with varying yields. We therefore wondered if Htt protein could be reliably measured in saliva. We assayed 98 saliva samples from manifest(HD), premanifest(PM), and age-matched normal control(NC) participants and found that salivary total Htt (tHtt) was significantly increased in HD saliva compared to NC. Salivary tHtt showed no gender effects and was significantly positively correlated with age in HD. As expected, tHtt levels had a positive correlation with motor symptoms and a negative correlation with cognitive ability and functional capacity in HD. Thus, tHtt protein can be reliably measured in human saliva and shows promise as a non-invasive clinically meaningful biomarker of disease progression in HD
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Salivary levels of total huntingtin are elevated in Huntington’s disease patients
Patients with Huntington's disease (HD), an autosomal-dominant neurodegenerative disease, show substantial variability in age-of-onset, symptom severity and course of illness, warranting the need for biomarkers to anticipate and monitor these features. The HD gene encodes the disease protein huntingtin (Htt), a potentially useful biomarker for this disease. In the current study, we determined whether total Htt protein (normal plus mutant; "tHtt") could be reliably measured in human saliva, a body fluid that is much more accessible compared to cerebral spinal fluid or even blood, and whether salivary levels of tHtt were clinically meaningful. We collected 146 saliva samples from manifest HD patients, early-premanifest individuals, late-premanifest patients, gene-negative family members and normal controls. We found that tHtt protein could be reliably and stably detected in human saliva and that tHtt levels were significantly increased in saliva from HD individuals compared to normal controls. Salivary tHtt showed no gender effects, nor were levels correlated with total protein levels in saliva. Salivary tHtt was significantly positively correlated with age, but not age-of-onset or CAG-repeat length. Importantly, salivary tHtt was significantly correlated with several clinical measures, indicating relevance to disease symptom onset and/or severity. Measurements of salivary tHtt offer significant promise as a relevant, non-invasive disease biomarker for HD, and its use could be implemented into clinical applications
Recommended from our members
Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington's Patients.
Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology