In our previous studies, we demonstrated that the products of alternative cleavage of non-APP substrates (known as Alcs) by γ-secretase gave rise to a modified p3-Alcα peptide profile in media conditioned by transfected cells expressing an FAD-linked mutant PS1 and a similar modified profile was also identified in the CSF of subjects with sporadic MCI (known as CDR 0.5 in Cohort 2 and recently renamed “prodromal AD” in the revised lexicon for dementia syndromes [21]), and mild AD [5,14]. The gene discussed is PSEN1; the disease is Alzheimer disease.