LAUSR

Recently, the Huntington ’ s Disease (HD) Integrated Staging System (HD-ISS) was developed as a new framework to standardize clinical research for HD. 1 Nevertheless, HD patients can show variable performance in certain tests at a particular visit, therefore not always consistently meeting the criteria for one or the other disease stage. This also includes the prediction of onset and severity of HD in premotor individuals. In this study (local ethics committee approval: AN1979 336/4.19401/5.10, 4464a), we aimed to better characterize biomarker changes in different disease stages of HD, including serum neuro fi lament light (sNFL) and clinical biomarkers including olfaction and cognitive tests. To this end, genetically con fi rmed HD patients (n = 54) and premotor HD mutation carriers (preHD; n = 19; ie, without distinct motor symptoms) were consecutively recruited during their routine follow up visits. Results were compared with HD-unaffected participants (healthy controls, HC). Group comparisons of demographic and all clinical as well as sNFL levels are summarized in the supplementary material. We found signi fi cant differences between controls and preHD participants in sNfL levels and odor identi fi cation, but no difference in cognitive tasks. preHD near to estimated disease onset (NEAR-preHD) based on group median for years to predicted disease onset age using a universal prediction model, 2 but not preHD far to estimated disease onset (FAR-preHD) showed signi fi cantly