Finding risk factors

摘要

Headlines trumpet the discovery of genes associated with Alzheimer's disease so often that one might think the genetic foundations of the disease must surely be mapped out in their entirety. Certainly for those who develop the early onset, or familial, form of the disease in late middle age, the lions share of the blame can be attributed to three genes: APP, PSEN1 and PSEN2. Each of these genes plays a role in producing amyloid-|3, the accumulation of which is widely thought to trigger the disorder's characteristic neurodegeneration. However, more than 90% of Alzheimer's cases are of the late-onset form, which typically manifests in people older than 65 years and seems to have a separate pool of genetic risk factors. Efforts to identify factors directly involved in the processing and accumulation of amyloid-(3 have yielded at least a dozen candidate genes implicated in this form of the disease, but their roles are still unclear and their total contribution cannot account for the estimated 60-80% hereditary risk of late-onset disease1.