Lastly, the biological effect of the p.Tyr167* mutation as a loss of function was supported by a 50% decrease of all ADAM10 isoforms in CSF of mutant cases as compared to controls, as well as a significant reduction of CSF sAPPα—around 70% as compared to controls and sporadic AD cases—which was consistent with a decrease of the α-secretase pathway processing of APP. The gene discussed is ADAM10; the disease is Alzheimer disease.