APP and early-onset autosomal dominant Alzheimer disease: Yet it must be noted that in the case of the study of a familial autosomal dominant Alzheimer's disease cohort by Chhatwal et al. (2013), and in the case of people with Down's syndrome as in the present study, the onset of Alzheimer's disease neuropathology is a near certainty provided that the required mutation or additional copy of APP is present, and therefore may represent a qualitatively different population to those with other risk factors such as APOE ε4 alleles, which are not determinant but greatly increase risk.