MAPT and Alzheimer disease: Although in a study on a Tg2576 transgenic mouse model of AD, there was no reduction in the brain Aβ burden, sildenafil was found to reduce tau hyperphosphorylation, decrease the activity of GSK 3β (GSK3β) and cyclin-dependent kinase 5 (CDK5) (p25/p35 ratio), increase the levels of brain-derived neurotrophic factor (BDNF), and increase the activity of Arc [47].