Figure 4.

Establishing causality. Although an isolated molecule might be linked to a disease, concluding that the molecule plays a causal role in disease pathogenesis is prohibited by the correlational nature of microarray. The results of three experimental approaches can lend support to claims of molecular causality: A, First, the candidate molecule, or the molecular pathway to which it belongs, can be systematically manipulated in cell culture, measuring a meaningful biochemical readout. For example, manipulating a molecule that is thought to be pathogenic in Alzheimer's disease should affect the levels of Aβ peptide. B, Second, the candidate molecule, or the molecular pathway to which it belongs, can be manipulated in animal models using transgenic technologies. In the case of Alzheimer's disease, this manipulation should phenocopy the behavioral, electrophysiological, and biochemical phenotype of Alzheimer's disease. C, Finally, genomic screens can be performed in humans, testing whether polymorphisms in the molecular pathway increase the risk of Alzheimer's disease.