In addition, the increased activity of BACE1 could also lead to β-cleaved carboxy-terminal fragment of β-Amyloid precursor protein (APP-βCTF) induced dysfunction of endosomes in AD. Endosomes are highly active β-Amyloid precursor protein (APP) processing sites, and endosome abnormalities are associated with upregulated expression of early endosomal regulator, rab5. These are the earliest known disease-specific neuronal response in AD. Increased activity of BACE1 leads to synthesis of the APP-βCTF. An elevated level of βCTF then causes rab 5 overactivation. βCTF recruits APPL1 to rab5 endosomes, where it stabilizes active GTP-rab5, leading to pathologically accelerated endocytosis, endosome swelling and selectively impaired axonal transport of rab5 endosomes.