You can take the genome out of the organism, but can you take the organism out of the environment?

Abstract

In a debate held on July 28th in Cincinnati, a new chapter in the nature versus nurture saga was initiated. The premise under discussion was whether nonfamilial, i.e. sporadic, Alzheimer disease (AD) is primarily a genetic disorder. The participants took the position that either A) genetic factors are largely responsible for the so-called sporadic cases of AD or B) environmental factors contribute to the development of sporadic AD. The argument that genetic factors result in sporadic AD was based on population based studies such as the Nun study and twin studies. The participants correctly point out the more than passing role of the APOE-e4 in the development of Alzheimer disease. In addition, a wide variety of genes and chromosomal loci have been implicated in the development of Alzheimer disease. However, although twin studies, for example, indicate a heritability of greater than 60% it is not 100%. The typical argument employed to explain this type of discrepancy is that when age corrected we get much closer since one of the siblings may die of other causes before having the “opportunity” to develop Alzheimer disease. While admitting that diet and other health related activities may influence the development of Alzheimer disease they maintain their position that non-familial Alzheimer disease is largely the result of genetics. On the other hand, the other participants argue that non-genetic factors play an important role in nonfamilial Alzheimer disease. Some of the possible factors include viruses, dietary components and metals. The unifying feature is postulated to be inflammation resulting from any of these insults. Special attention was paid to the role of aluminum, which has long been conjectured to facilitate the development of Alzheimer disease. In addition, the role of diet and especially dietary fats were discussed. With the increasing evidence of oxidative stress in the etiology of Alzheimer disease, the authors also consider the role of trace metal deposition through dietary exposure. Finally, increasing evidence in a number of chronic conditions has implicated bacterial and viral pathogens as underlying components in disease etiology. HSV-1 has been implicated as a potential underlying component in Alzheimer disease. Thus, these authors hold that environmental concerns play a large role in the development of Alzheimer disease and moreover are more tractable to intervention that are genetic predispositions. So, what can we take away from this? It is clear that genetic predisposition is important in the development of disease and that the development of disease can be modified by controlling external influences, i.e. cholesterol uptake. However, the important issue from the perspective of the prospective patient, current patient, or family members is what can we predict about the natural history of the individual. The studies listed