How Mn-triggered microglial IL-1β and TNF-α release subsequently increases APP production, BACE1 expression, and β-secretase activity (amyloidogenic) and decreases ADAM10/a-secretase activity (non-amyloidogenic) are currently not known, and even how Mn treatment affects IL-1β and TNF-α release was not settled in previous studies with conflicting results from cell and animal AD models (Domingues et al., 2017). This evidence concerns the gene APP and Alzheimer disease.