Josefine Waldthaler

There is increasing evidence suggesting that the clinical presentation of Parkinson´s disease (PD) is influenced by complex interactions between neurodegeneration and potentially counteracting mechanisms. However, these compensatory mechanisms have not received much attention in terms of their potential therapeutic value. studies examining the interaction between nigrostriatal degeneration and cerebral compensation and its failure as a potential driver of early-stage PD symptoms and progression are lacking.Our multinational consortium, comprised of experts in molecular and structural brain imaging and neurophysiology with extensive research experience in movement disorders, aims to address this gap. Together, we have developed five work packages that primarily focus on analysing multimodal imaging data in existing cohorts of early PD patients. Our goal is to identify neurobiological patterns that characterise early PD and how nigrostriatal neurodegeneration and cerebral counteracting mechanismscontribute to specific features of early disease, such as motor or cognitive symptom burden. By validating these emerging concepts with cross-national data and protocol sharing, our aim is to establish a foundation for staging models that integrate both neurodegenerative and compensatory aspects of the brain. Additionally, these findings may enhance the translational potential of possible therapies that target both processes.