The major argument in favor of using pathological criteria for the definition of disease is an analogy: in Alzheimer disease, the loci identified for the disorder, APP, and the presenilins clearly map into one pathway (Hardy and Selkoe, 2002): defining the disease clinically would lead to confusion with a large series of other genes (MAPT, PRNP, PGRN, etc.)being grouped with them. This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.