Our data, obtained in a pre-symptomatic model with no detectable alpha-synuclein aggregates and no indication of a shifted cell type composition due to neuronal loss further strengthens the emerging concept from an increasing number of reports that glial cell activation is a contributing factor in early stages of disease unfolding rather than a consequence of aggregate formation in later stages of the pathogenesis (Halliday and Stevens, 2011), an idea also put forward for Alzheimer's disease (Hong et al., 2016). The gene discussed is SNCA; the disease is Alzheimer disease.