Parkinson’s disease (PD) is characterized by a temporal caudal-rostral progression of Lewy body (LB) pathology across a selected set of nuclei in the brain1. The distribution pattern of LB pathology is divided into six Braak stages based on accumulation of the protein α-synuclein—the main component of LBs and Lewy neurites—in the brainstem, limbic, and neocortical regions1. These six Braak stages indicate affected regions throughout the progression of PD with the region involved in Braak stage 1 being first affected and the region involved in Braak stage 6 being last affected. Thus, the Braak staging scheme points out vulnerable brain regions involved in disease progression and the sequential order of their vulnerability. Different hypotheses have been brought forward to explain the evolving LB pathology across the brain, including: retrograde transport of pathological α-synuclein via neuroanatomical networks, α-synuclein’s prion-like behavior, and cell- or region-autonomous factors2,3. Yet, the mechanisms underlying the selective vulnerability of brain regions to LB pathology remain poorly understood, limiting the ability to diagnose and treat PD.
