APP and Cognitive impairment: RAB5 is aberrantly activated by APP-βCTF (secretase-cleaved C-terminal fragment (CTF) of amyloid precursor protein (APP)), and the transgenic expression of activated RAB5 in mouse neurons led to the enlargement and mistrafficking of early endosomes, as well as synaptic plasticity deficits, tau hyperphosphorylation, and cognitive deficits [8,10,11].