An Important Finding in Huntington Disease
An Important Finding in Huntington Disease
Rosas HD, Chen YI, Doros G, et al
Arch Neurol. 2012;69:887-893
Abnormal accumulation of transition metals in the brain has been implicated early on in the pathogenesis of Huntington disease and certain other neurodegenerative disorders. Using advanced MRI methods, Rosas and colleagues, in this observational study, aimed to comprehensively assess and confirm the distribution of metal deposition in the brain from preclinical through symptomatic stages of Huntington disease.
To quantify the phase evolution, susceptibility-weighted MR images were obtained from 28 Huntington disease expanded gene carriers, 34 participants with symptomatic Huntington disease, and 56 age- and sex-matched healthy control patients. At autopsy, brain concentrations of transition metals were measured using inductively coupled plasma mass spectrometry.
Patients with Huntington disease had progressive increases in phase evolution in the basal ganglia, beginning preclinically long before anticipated disease onset and increasing as the disease process evolved. In the cerebral cortex, increases were seen only in specific regions (sensorimotor, parietal, and occipital) and only in symptomatic patients. Increases were associated not only with excessive accumulation of brain iron stored within ferritin but also with complex changes in other transition metals.
These findings suggest complex, early changes in metal homeostasis underlying the pathogenesis of Huntington disease. If confirmed, these results may have profound clinical implications not only for Huntington disease but also for other neurodegenerative disorders. MRI measurement of metals could provide useful markers of disease progression and response to therapy, and metals could even be potential therapeutic targets. Future research should include comprehensive evaluation of metal absorption, transport, and storage mechanisms as well as of metalloprotein regulation.
Abstract
Alterations in Brain Transition Metals in Huntington Disease: An Evolving and Intricate Story
Rosas HD, Chen YI, Doros G, et al
Arch Neurol. 2012;69:887-893
Study Summary
Abnormal accumulation of transition metals in the brain has been implicated early on in the pathogenesis of Huntington disease and certain other neurodegenerative disorders. Using advanced MRI methods, Rosas and colleagues, in this observational study, aimed to comprehensively assess and confirm the distribution of metal deposition in the brain from preclinical through symptomatic stages of Huntington disease.
To quantify the phase evolution, susceptibility-weighted MR images were obtained from 28 Huntington disease expanded gene carriers, 34 participants with symptomatic Huntington disease, and 56 age- and sex-matched healthy control patients. At autopsy, brain concentrations of transition metals were measured using inductively coupled plasma mass spectrometry.
Patients with Huntington disease had progressive increases in phase evolution in the basal ganglia, beginning preclinically long before anticipated disease onset and increasing as the disease process evolved. In the cerebral cortex, increases were seen only in specific regions (sensorimotor, parietal, and occipital) and only in symptomatic patients. Increases were associated not only with excessive accumulation of brain iron stored within ferritin but also with complex changes in other transition metals.
Viewpoint
These findings suggest complex, early changes in metal homeostasis underlying the pathogenesis of Huntington disease. If confirmed, these results may have profound clinical implications not only for Huntington disease but also for other neurodegenerative disorders. MRI measurement of metals could provide useful markers of disease progression and response to therapy, and metals could even be potential therapeutic targets. Future research should include comprehensive evaluation of metal absorption, transport, and storage mechanisms as well as of metalloprotein regulation.
Abstract
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