The discovery of pathogenic mutations in the amyloid precursor protein gene in families with Alzheimer's disease is a major advance in the understanding of the pathogenesis of Alzheimer's disease. In certain families at least, beta-amyloid metabolism plays a central role in the disease process. It is tempting to speculate that beta-amyloid is common to the majority of Alzheimer cases. In the immediate future the discovery of the mutations responsible for the condition in those families that show linkage to chromosomes 14 and 19 will enable it to be established whether beta-amyloid is involved in these pedigrees as well. If amyloid metabolism is involved in APP and chromosomes 14 and 19 families, it suggests that Alzheimer's disease is a single disease with a common metabolic pathway. However, if other mechanisms are implicated, evidence is provided that Alzheimer's disease is a heterogeneous disorder that shares common clinicopathological features.