Although the effects of osmotic pump delivery of TKIs on microgliosis (Dhawan & Combs, 2012), Aβ pathology (Cancino et al, 2008) and parkin relationship with amyloid accumulation (Perucho et al, 2010) were previously reported in AD models, our results identified novel mechanisms involving TKI-mediated autophagic clearance of intraneuronal Aβ and Tau and demonstrated the effects of brain-penetrant TKIs (Bosutinib and Nilotinib) in improving amyloid pathology and cognition. This evidence concerns the gene PRKN and Alzheimer disease.