Bertoglio, Daniele

Everix, Liesbeth

Staelens, Steven

Abstract: Huntington\u2019s disease (HD) is a rare, autosomal, and dominantly inherited neurodegenerative disease characterized by aggregation of mutated Huntingtin protein (mHTT). People with HD (pwHD) suffer from progressive neuronal cell loss in the striatum and cortex, causing progressive motor impairments, psychiatric symptoms, and cognitive impairment. HD symptoms can partially be explained by the disruption of a wide variety of molecular processes. Monitoring molecular changes may provide useful insights to track disease progression or to assess therapeutic efficacy. The purpose of this chapter is to provide a state-of-the-art overview of the biomarkers known to be altered in HD, together with their associated positron emission tomography (PET) radioligands. PET imaging allows non-invasive mapping of biomarker distribution with high spatial resolution and sensitivity. To date, over 50 PET studies in pwHD have been performed, most of which have claimed subclinical biomarker (e.g. phosphodiesterase 10a, dopaminergic receptors) impairment before the appearance of overt HD symptoms. This finding stresses the importance of early detection and potential intervention, decades before age of onset. In addition, we report on the advances on the first radioligands targeting mHTT aggregates, some of which are already under clinical evaluation

Positron Emission Tomography (PET) imaging biomarkers in Huntington\u2019s disease

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