Finally, to fully appreciate the causal role of changes in ubiquitin-dependent proteostasis at prodromal stage of AD neuropathology, it’s important to notice that the concentration of ubiquitin and UCHL-1 has been reported to increase in cerebrospinal fluid (CSF) from subjects with AD (Kandimalla et al., 2011; Oeckl et al., 2014; Heywood et al., 2015; Sjödin et al., 2017). This evidence concerns the gene UCHL1 and Alzheimer disease.