New insights into genetic aspects of Alzheimer's disease. Does genetic information make a difference in clinical practice?
Genetic testing sometimes offers definitive information for patients who have a family history of early-onset Alzheimer's disease that occurs before age 50 in a Mendelian pattern. However, for patients who are already symptomatic, especially those with sufficient symptoms to warrant a clinical diagnosis of Alzheimer's disease, genetic testing may not contribute a great deal of information beyond that already available from the clinical and family history. For prediction of disease onset, genetic testing can sometimes give a clear picture of disease risk, but each patient must carefully weigh the risks and benefits of having that information. For early-onset Alzheimer's disease occurring beyond age 50 or without a clear Mendelian pattern, genetic testing is unlikely to be informative. In patients who have a family history of late-onset Alzheimer's disease, while APOE's contribution to increased risk is indisputable, its potential use as a genetic test is very limited. Testing may be helpful as an adjunct to clinical diagnosis but does not obviate the need for a full workup for treatable causes. Thus, the benefit of testing may be marginal. No consensus has been reached as to the value of genetic testing for early detection of late-onset disease, but APOE testing might become important in the future if it helps to define the need for intervention or to select an optimal intervention. There is a broad consensus that APOE testing lacks sufficient predictive value to be suitable for predictive testing in asymptomatic persons.
Blacker
D
D
Harvard Medical School, Gerontology Research Unit, Massachusetts General Hospital East, Boston, USA. blacker@psych.mgh.harvard.edu
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D005817:Genetic Counseling; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D012307:Risk Factors; D012680:Sensitivity and Specificity
D001057:Apolipoproteins E