Identifying the earliest biochemical changes that occur in sporadic Parkinson’s disease (PD) is crucial to gaining insights into its pathogenesis. Christina Toomey, PhD, UCL Queen Square Institute of Neurology, London, UK, discusses an investigation into the underlying changes in sporadic PD, using large-scale protein expression profiling in 9 Braak brain regions along a gradient of unaffected-severe pathology. The study found mitochondrial dysfunction in all 9 regions. Mitochondrial protein expression changes were found to follow the gradient of unaffected-severe disease. Additionally, these alterations were seen before the emergence of α-synuclein pathology, identifying mitochondrial dysfunction as a hallmark of early disease. This interview took place during the AD/PD™ 2021 conference.