Non-familial Alzheimer's disease is mainly due to genetic factors

This team takes the position that what is commonly referred to as non-familial Alzheimer's disease (AD) is predominantly due to genetic factors. Population-based studies suggest that genetic factors cause the majority of cases that begin after age 60. There are several lines of evidence supporting this position: - Data from the Nun Study suggest that the risk for AD is largely established by early adulthood, implying that later adult exposures likely play only a small role in causation. - Family studies show that first-degree blood relatives of persons with non-familial AD have a substantially increased risk of AD relative to controls. - Twin studies suggest that the heritability of AD exceeds 60%. - Environmental factors, such as socioeconomic status, education, and head injury, are strong risk factors for AD only in individuals with a genetic predisposition. - The APOE genotype is a powerful risk factor for AD and accounts for as much as 50% of AD in many populations. - There are numerous other candidate genes with strong associations with AD that presumably explain the remaining population risk. This paper further reviews the mechanisms associated with AD causation for APOE and other candidate genes and implications for the development of prevention strategies.