The aim of the present study was (1) to strengthen our previous findings (Humpel, 2015b) that neprilysin can clear plaques in adult brain slices, and test if a collagen hydrogel can provide a more stable application form, (2) to explore if platelets loaded with neprilysin can be an alternative strategy to clear plaques in brain slices, and (3) finally to translate these findings into in vivo mouse models and test if intranasal applications can clear plaques in transgenic AD mice. Here, MME is linked to Alzheimer disease.