We have previously demonstrated that the reduction of α-secretase activity is central in early stages of AD pathogenesis and is a consequence of a failure in ADAM10 exocytosis/endocytosis processes.7, 9 Here we describe a significant decrease in PKC-dependent phosphorylation of SAP97 T629 in AD patients' hippocampi, an outcome in line with previous studies revealing that AD patients have lower levels of PKC activity.30 Moreover, this alteration is not associated with the presence of genetic variations in the SH3 domain of SAP97. This evidence concerns the gene DLG1 and Alzheimer disease.