Positron emission tomography imaging to detect synaptic damage in early or premanifest Huntington’s disease

Takeaway

  • The onset of Huntington’s disease (HD) can be predicted prior to the development of movement disorder, by detecting synaptic damage in the specific regions of the brain using focused imaging, in patients with early or premanifest HD.

Why this matters

  • Loss of striatal medium spiny neurons (MSNs), as well as loss of neurons from other regions of the brain, are key features of Huntington’s disease (HD), an autosomal disorder caused by a mutated HTT gene.

  • Signs of synaptic dysfunction in patients with early HD can be observed in positron emission tomography (PET) and magnetic resonance imaging (MRI) scans, including alterations in synaptic proteins leading to degenerated MSNs, synaptic disconnection between cerebral cortex and striatum, and striatal glucose hypometabolism. However, direct in vivo evidence to detect early synaptic damage in mutated HTT carriers is still lacking.

  • The synaptic vesicle protein 2A (SV2A) is ubiquitously present in presynaptic terminals throughout the brain and can be viewed using its PET radioligand 11C-UCB-J, to detect the extent of synaptic damage.