Predictive value of APOE genotyping in incipient Alzheimer's disease

The Mayo Alzheimer's Disease Center/Alzheimer's Disease Patient Registry is a prospective, longitudinal project of aging and dementia in a community setting. Over 400 pairs of individuals have been studied through this project, and extensive data on clinical, radiological, neuropathological, and biological variables have been gathered. Previous case-control studies on this group of subjects have documented the role of the apolipoprotein E (APOE) ε4 as a risk factor for dementia. Subsequent analyses between APOE and the age of the patients with dementia have shown that most of the ε4 effect is manifest in subjects under 75 years of age. We have also used this patient resource to study a group of individuals who are at risk for dementia by virtue of having a significant memory impairment. We have designated these patients as having a mild cognitive impairment because they have abnormal memory function but do not reach criteria for dementia. Over the course of several years of follow-up, these subjects evolve to dementia at a rate of approximately 15% per year. The presence of an APOE ε4 carrier status is the best predictor of subsequent development of dementia in these individuals. These studies indicate that APOE is an important risk factor for AD, and in patients with a mild cognitive impairment, APOE may be useful in predicting who is likely to progress to dementia.