Staging of Lewy pathology according to the Braak model. Schematic summarizing the progression of Parkinson’s disease as proposed by Braak and colleagues . According to the Braak model, αsyn deposits in specific brain regions and neuronal types giving rise to Lewy pathology in a stereotypic, temporal pattern that ascends caudo-rostrally from the lower brainstem (including the dorsal motor nucleus of the vagus nerve in the medulla then the coeruleus-subcoeruleus complex, raphe nuclei, gigantocellular reticular nucleus in the medulla aand pons) through susceptible regions of the midbrain (substantia nigra and the pedunculopontine tegmental nucleus) and forebrain (e.g., amygdala) and into the cerebral cortex (e.g., anteromedial temporal mesocortex, cingulate cortex and later neocortical structures). It is hypothesized that the disease initiates in the periphery, gaining access to the CNS through retrograde transport along projection neurons from the gastrointestinal tract. As the disease progresses, the severity of lesions in the susceptible regions increases.