APP and Alzheimer disease: Additional studies have revealed that decreased expression of the ubiquitin E3 ligases Parkin and HRD1 (E3 ubiquitin protein ligase HRD1) is a common observation in AD specimens, which reduces the degradation of APP thereby increased the amount of its cleaved Aβ (Nomura, Hosoi, Kaneko, Ozawa, & Nishi, 2016).