SNCA and Parkinson disease: Axonal pathology has been demonstrated prior to dopaminergic neuronal loss in animal22 56 and cell models.57 Alpha-synuclein plays a role in axonal growth with higher density, thinner axons seen in the brain of patients with early PD.58 Imaging biomarkers that assess white matter integrity such as fixel-based analysis might be more sensitive at picking up anatomical abnormalities at the earliest stages of PD; our findings support this.