The papers selected by the Journal of Alzheimer's Disease for commentary cover three interlinked areas of research: the search for genetic susceptibility of trait markers, the search for biomarkers or state markers, and the search for novel therapeutic targets through an understanding of the mechanisms of disease. This work is reviewed and some directions of travel for the next phase of research suggested. Specifically both state and trait marker research will benefit from advances in technology but will require, on the one hand, larger sample sets and, on the other, the use of study designs other than case-control. Routine collection of data through the electronic medical record coupled with samples collected in clinical care represents a major opportunity to scale these studies. Success in identifying trait markers for stratification and state markers for experimental medicine may be necessary to exploit the increased understanding of mechanisms and the new therapeutic opportunities this is allowing.