%X In this article, we first present a summary of the general assumptions about Down syndrome (DS) still to be found in the literature. We go on to show how new research has modified these assumptions, pointing to a wide range of individual differences at every level of description. We argue that, in the context of significant increases in DS life expectancy, a focus on individual differences in trisomy 21 at all levels-genetic, cellular, neural, cognitive, behavioral, and environmental-constitutes one of the best approaches for understanding genotype/phenotype relations in DS and for exploring risk and protective factors for Alzheimer's disease in this high-risk population. %L discovery1481543 %A A Karmiloff-Smith %A T Al-Janabi %A H D'Souza %A J Groet %A E Massand %A K Mok %A C Startin %A E Fisher %A J Hardy %A D Nizetic %A V Tybulewicz %A A Strydom %J F1000Research %O Copyright © 2016 Karmiloff-Smith A et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. %V 5 %C England %D 2016 %K Alzheimer’s disease, Down syndrome, neurodevelopmental disorder, trisomy 21 %T The importance of understanding individual differences in Down syndrome