Susceptibility gene(s) forAlzheimer's disease on chromosome 10

The majority of Alzheimer's disease is inherited in a complex manner involv ing environmental factors and several genes. One of these genes is Apolipop rotein E where the polymorphic allele (APOE epsilon4) has been robustly sho wn to modify risk and the course of Alzheimer's disease. The epsilon4 allel e however, only accounts for similar to 50% of late onset Alzheimer's disea se. Here we review three quite different approaches that have led to convin cing evidence that there is at least one other susceptibility gene for comp lex inherited forms of Alzheimer's disease on chromosome 10q. Two linkage s tudies give strong evidence of a locus at almost exactly the same location: one using the amyloid beta brain-deposited fragment of the amyloid precurs or protein as a continuous phenotype, and the other using a categorical dis ease phenotype. A third candidate gene linkage and association analysis app roach interestingly finds a maximum signal similar to 35-60cM distal to the previous studies.