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IMAGING EPIGENETICS IN THE HUMAN BRAIN WITH THE NOVEL [11C]MARTINOSTAT PET IN PRECLINICAL AD, MCI, AD, AND FRONTOTEMPORAL DEMENTIA INDIVIDUALS

      [11C]Martinostat is a novel PET imaging agent that selectively binds to the Histone deacetylases (HDACs) class I and allows for the first time the assessment of epigenetic mechanisms in the brain in vivo. Reduced HDAC levels lead to a configuration of an open-chromatin structure, increasing genes’ expression. In pharmacological doses, [11C]Martinostat induces changes in genes associated with plasticity (e.g. BDNF and SYP(synaptophysin)) and neurodegeneration (e.g. Progranulin). Since epigenetic changes have been theoretically proposed as part of AD pathogenesis, here, we imaged epigenetic changes in patients with dementia for the first time. We hypothesised that [11C]Martinostat uptake is abnormal in individuals with AD and that this abnormality is related with amyloid and tau levels.
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