PET Imaging of Epigenetic Influences on Alzheimer’s Disease

Abstract

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, [18F]FAHA demonstrates sites of differential HDAC activity, [18F]FDG indirectly illuminates sites of neuronal hypomethylation, and the carbon-11 isotope-containing Pittsburgh compound B ([11C]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.

Nalmefene is effective at reducing alcohol seeking, treating alcohol‐cocaine interactions and reducing alcohol‐induced histone deacetylases gene expression in blood

“…et al , 2013), and many efforts are currently being deployed to investigate their role as possible biomarkers. For instance, several PET radiotracers have been developed for visualizing HDAC activity in Alzheimer's disease (Couto and Millis, ) although gene expression from peripheral blood is one of the most promising biomarkers (Mizuarai et al , ). Furthermore, pharmacological treatments are able to alter the activity of HDACs.…”

18F-FNDP for PET Imaging of Soluble Epoxide Hydrolase

“…Clinically stroke is evaluated primarily through anatomic and functional magnetic resonance imaging, with molecular approaches limited due to a lack of viable radiotracers for this indication beyond those used to measure perfusion with single photon emission computed tomography (15). A PET agent for sEH may enable distinction between AD and VCI in vivo, rather than having to rely on postmortem observation of Aβ plaques and neurofibrillary tangles (16,17). …”

Radiosynthesis and preliminary evaluation of an18F‐labeled tubastatin A analog for PET imaging of histone deacetylase 6

“…18,19 HDAC6 also has a binding domain against the cytoskeletal motor protein dynein and couples ubiquitinated proteins to dynein motors, thereby mediating their transport along microtubules to aggresomes. [24][25][26] Besides the detection of regions with abnormalities in HDAC expression levels, PET imaging can contribute to the development of HDAC inhibitor drugs by enabling the assessment of target engagement. 23 In the past decade, a number of radiolabeled HDAC ligands for positron emission tomography (PET) imaging have been developed.…”

“…23 In the past decade, a number of radiolabeled HDAC ligands for positron emission tomography (PET) imaging have been developed. [24][25][26] Besides the detection of regions with abnormalities in HDAC expression levels, PET imaging can contribute to the development of HDAC inhibitor drugs by enabling the assessment of target engagement. 27,28 The majority of HDAC radioligands, including the first SAHA-based HDAC radioligand [ 18 F] FAHA, are hydroxamic acid based with others being benzamide based or carboxylic acid based.…”