Huntington's disease (HD)

Huntington's disease is an inherited (autosomal dominant), progressive neurodegenerative disorder caused by cytosine-adenine-guanidine (CAG) trinucleotide repeat expansion in huntingtin gene, which leads to forming of intranuclear inclusions of mutated huntingtin (mHTT) protein. The symptoms of HD include motor dysfunction, cognitive decline, and psychiatric disturbances. The onset of notable symptoms usually occurs at the age of mid-40s. Neuronal degeneration is heterogeneous leading to variable symptom profile.

Specific mHTT targeting PET radioligands are under development (Herrmann et al., 2021; Kaur et al., 2021; Liu et al., 2020; Bertoglio et al., 2022a). [11C]CHDI-180R has high affinity and selectivity for mHTT aggregates, allowing non-invasive in vivo assessment of mHTT in the brain (Bertoglio et al., 2022b; Delva et al., 2022).

Changes in metabolism and neurotransmission, and neuroinflammation, can be studied with PET (Roussakis & Piccini, 2015; Pagano et al., 2016; Niccolini et al., 2018).

Reduced SV2A binding, suggesting synaptic damage, has been observed in in putamen, caudate, pallidum, cerebellum, and parietal, temporal, and frontal cortices in early HD, using [11C]UCB-J PET (Delva et al., 2021). In mouse model of HD, reduction of [11C]UCB-J binding has been seen in brain and spinal cord (Bertoglio et al., 2022c).

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Everix L, Staelens S, Bertoglio D. Positron Emission Tomography (PET) Imaging Biomarkers in Huntington’s Disease. In: Thomas EA, Parkin GM (eds) Biomarkers for Huntington's Disease. Contemporary Clinical Neuroscience. Springer, 2023. doi: 10.1007/978-3-031-32815-2_6.

Nana AL, Kim EH, Thu DC, Oorschot DE, Tippett LJ, Hogg VM, Synek BJ, Roxburgh R, Waldvogel HJ, Faull RL. Widespread heterogeneous neuronal loss across the cerebral cortex in Huntington's disease. J Huntingtons Dis. 2014; 3(1): 45-64. doi: 10.3233/JHD-140092.

Niccolini F, Pagano G, Fusar-Poli P, Wood A, Mrzljak L, Sampaio C, Politis M. Striatal molecular alterations in HD gene carriers: a systematic review and meta-analysis of PET studies. J Neurol Neurosurg Psychiatry 2018; 89(2): 185-196. doi: 10.1136/jnnp-2017-316633.

Tabrizi SJ, Flower MD, Ross CA, Wild EJ. Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat Rev Neurol. 2020; 16(10): 529-546. doi: 10.1038/s41582-020-0389-4.

Waldvogel HJ, Kim EH, Tippett LJ, Vonsattel JP, Faull RL. The neuropathology of Huntington's disease. Curr Top Behav Neurosci. 2015; 22: 33-80. doi: 10.1007/7854_2014_354.


Updated at: 2023-10-19
Created at: 2022-02-04
Written by: Vesa Oikonen