Several potential biological mechanisms have been proposed to explain this link, including chronic neuroinflammation, metabolic dysregulation, and pathological upregulation of several key PD-linked proteins, including alpha-synuclein, hyperphosphorylated tau, amyloid precursor protein, TDP-43 and, more recently, leucine-rich repeat kinase 2 (LRRK2) and its Rab protein substrates [see Delic et al. for review (151)]. This evidence concerns the gene SNCA and Parkinson disease.