Rubinsztein and Easton report the results of a meta-analysis of studies on the association between Alzheimer's disease risk and genotype for apolipoprotein E (apoE; see Alzheimer's disease summary for further background information) [Rubinsztein, D. and Easton, D.F. (1999) Dement Geriatr Cogn Disord 10, 199-209 (Abstract)]. They find "overwhelming" evidence that the apoE4 variant is a risk factor for both early- (under 65 years) and late-onset disease, calculating that overall 60% of late-onset cases and 92% of early-onset cases are attributable to apoE (in other words, these are the percentages of cases that would be avoided if all individuals carried a low-risk genotype). In cases where there was clear familial aggregation of disease, however, the contribution of apoE genotype was smaller, particularly in the case of early-onset disease; this is presumably because other known factors such as APP and presenilin mutations make a substantial contribution to early-onset familial disease. The calculated odds ratios for the homozygous apoE4/apoE4 genotype compared with apoE3/apoE3 were 11.57 for late-onset and 61.44 for early-onset disease. The evidence in favour of a possible protective role for the apoE2 allele is more equivocal: although there was a reduced odds ratio of 0.68 for late-onset disease, the odds ratio was actually slightly higher (1.70) for early-onset familial disease.
Comment: There now seems no doubt that the apoE4 allele, particularly in its homozygous state (a genotype carried by an estimated 2% of white people of European descent) is a substantial risk factor for Alzheimer's disease. At this stage, in the absence of effective treatment or prophylaxis, there is no way of using this knowledge to prevent disease. It is also important to emphasise that many people who carry the apoE4 allele do not develop Alzheimer's, so there must be other genetic and/or environmental factors involved. Nevertheless, the hope for the future must be that biochemical studies will reveal how apoE is involved in the processes that go awry in Alzheimer's, and perhaps lead to development of an effective intervention. If prophylaxis ever becomes possible, it might then be worth knowing one's apoE genotype.