PET Imaging of Epigenetic Influences on Alzheimer's Disease

The precise role of environment-gene interactions (epigenetics) in the development and progression of Alzheimer's disease (AD) is unclear. This review focuses on the premise that radiotracer-specific PET imaging allows clinicians to visualize epigenetically influenced events and that such imaging may provide new, valuable insights for preventing, diagnosing, and treating AD. Current understanding of the role of epigenetics in AD and the principles underlying the use of PET radiotracers for in vivo diagnosis are reviewed. The relative efficacies of various PET radiotracers for visualizing the epigenetic influences on AD and their use for diagnosis are discussed. For example, [(18)F]FAHA demonstrates sites of differential HDAC activity, [(18)F]FDG indirectly illuminates sites of neuronal hypomethylation, and the carbon-11 isotope-containing Pittsburgh compound B ([(11)C]PiB) images amyloid-beta plaque deposits. A definitive AD diagnosis is currently achievable only by postmortem histological observation of amyloid-beta plaques and tau neurofibrillary tangles. Therefore, reliable in vivo neuroimaging techniques could provide opportunities for early diagnosis and treatment of AD.