In this review, we have focused on several recent areas of new research: the role of ubiquitin C-terminal hydrolase L1 (Uch-L1), Ubiquitin-B+1 (UBB+1), F-box protein 2 (Fbxo2), and aggregation-promoting chaperones (CRAM-1 and MOAG-4) in Amyloid precursor protein (APP) and Aβ related metabolism as well as the related signaling pathways in AD and SCI, and discuss pressing questions in these fields of research. Here, APP is linked to Alzheimer disease.