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• W2101509528 abstract "<h3>Objective:</h3> To use in vivo neuroimaging and postmortem neuropathologic analysis in <i>C9orf72</i> repeat expansion patients to investigate the hypothesis that <i>C9orf72</i> promoter hypermethylation is neuroprotective and regionally selective. <h3>Methods:</h3> Twenty patients with a <i>C9orf72</i> repeat expansion participating in a high-resolution MRI scan and a clinical examination and a subset of patients (n = 11) were followed longitudinally with these measures. Gray matter (GM) density was related to <i>C9orf72</i> promoter hypermethylation using permutation-based testing. Regional neuronal loss was measured in an independent autopsy series (n = 35) of <i>C9orf72</i> repeat expansion patients. <h3>Results:</h3> GM analysis revealed that hippocampus, frontal cortex, and thalamus are associated with hypermethylation and thus appear to be relatively protected from mutant <i>C9orf72</i>. Neuropathologic analysis demonstrated an association between reduced neuronal loss and hypermethylation in hippocampus and frontal cortex. Longitudinal neuroimaging revealed that hypermethylation is associated with reduced longitudinal decline in GM regions protected by hypermethylation and longitudinal neuropsychological assessment demonstrated that longitudinal decline in verbal recall is protected by hypermethylation. <h3>Conclusions:</h3> These cross-sectional and longitudinal neuroimaging studies, along with neuropathologic validation studies, provide converging evidence for neuroprotective properties of <i>C9orf72</i> promoter hypermethylation. These findings converge with prior postmortem studies suggesting that <i>C9orf72</i> promoter hypermethylation may be a neuroprotective target for drug discovery." @default.
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• W2101509528 date "2015-03-20" @default.
• W2101509528 modified "2023-10-16" @default.
• W2101509528 title "C9orf72 promoter hypermethylation is neuroprotective: Neuroimaging and neuropathologic evidence" @default.
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• W2101509528 doi "https://doi.org/10.1212/wnl.0000000000001495" @default.
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