Even in the absence of overt PD or AD, NM-filled neurons from apparently healthy aged individuals also exhibit early signs of neuronal dysfunction and degeneration compared to young adult brains, including age-related loss of pigmented SNpc and LC neurons, downregulation of phenotypic neuronal markers, alpha-synuclein and tau pathology or the presence of extracellular NM (eNM) released from dying neurons associated with sustained microglial activation8–12. This evidence concerns the gene SNCA and Parkinson disease.