Alpha-synuclein (AS) is a presynaptic protein and arguably has the most central role in PD pathogenesis as: (1) multiplications and mutations of the AS gene (SNCA) locus cause familial PD [6,22], (2) aggregated AS is a major constituent of LBs and Lewy neurites, the pathological hallmark in AS-related PD and most idiopathic cases [23] and (3) AS can be secreted into the extracellular space and trans-synaptically “spread” to anatomically interconnected brain regions [24,25,26,27]. The gene discussed is SNCA; the disease is Parkinson disease.