In the search for new genes in Alzheimer's disease, classic linkage-based and candidate-gene-based association studies have been supplanted by exome sequencing, genome-wide sequencing (for mendelian forms of Alzheimer's disease), and genome-wide association studies (for non-mendelian forms). The identification of new susceptibility genes has opened new avenues for exploration of the underlying disease mechanisms. In addition to detecting novel risk factors in large samples, next-generation sequencing approaches can deliver novel insights with even small numbers of patients. The shift in focus towards translational studies and sequencing of individual patients places each patient's biomaterials as the central unit of genetic studies. The notional shift needed to make the patient central to genetic studies will necessitate strong collaboration and input from clinical neurologists.
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