One of the most exciting recent hypotheses in neurology is that most neurodegenerative diseases are caused by the neuron to neuron propagation of prion-like misfolded proteins. In Parkinson disease, the theory initially emerged from postmortem studies demonstrating a caudal-rostral progression of pathology from lower brainstem to neocortex. Later, animal studies showed that the hallmark protein of PD, α-synuclein, exhibited all the characteristics of a prion. Here, we describe our work using human neuroimaging to test the theory that PD pathology advances via a propagating process along the connectome. We found that the pattern and progression of brain atrophy follow neuronal connectivity, correlate with clinical features, and identify an epicenter in the brainstem.
Keywords: MRI; Parkinson disease; deformation brain morphometry; prion; α-synuclein.