Susceptibility gene(s) for Alzheimer's disease on chromosome 10

The majority of Alzheimer's disease is inherited in a complex manner involving environmental factors and several genes. One of these genes is Apolipoprotein E where the polymorphic allele (APOE epsilon 4) has been robustly shown to modify risk and the course of Alzheimer's disease. The epsilon 4 allele however, only accounts for approximately 50% of late onset Alzheimer's disease. Here we review three quite different approaches that have led to convincing evidence that there is at least one other susceptibility gene for complex inherited forms of Alzheimer's disease on chromosome 10q. Two linkage studies give strong evidence of a locus at almost exactly the same location: one using the amyloid beta brain-deposited fragment of the amyloid precursor protein as a continuous phenotype, and the other using a categorical disease phenotype. A third candidate gene linkage and association analysis approach interestingly finds a maximum signal approximately 35-60cM distal to the previous studies.