Apolipoprotein E genetic variation and Alzheimer's disease - A meta-analysis

In order to quantify the effects of apolipoprotein (apo) E on early- and late-onset, sporadic and familial Alzheimer's disease (AD) more precisely we performed a metaanalysis of 42 case-control series published before July 1996. We excluded studies of late-onset AD with fewer than 50 cases and 50 controls. The estimated odds ratio of AD over the age of 65 yea rs associated with the apo epsilon 4 allele, relative to apo epsilon 3, was 3.18 (95% CI 2.93-3.45, p < 0.00001). Apo epsilon 4 was associated with a significantly higher relative risk of early-onset disease (<65 years) unselected for family history (OR 4.86, 95% CI 3.61-6.54, p < 0.0001), but its impact on early-onset familial disease was weaker (OR 1.48, 95% CI 1.02-2.16). The estimated odds ratio associated with the epsilon 4/epsilon 4 genotype, relative to the epsilon 3/epsilon 3 genotype, was 11.57 (95% CI 8.67-15.44) for all cases over 65 and 61.44 (95% CI 13.47-280.3) for early-onset disease unselected for family history. Apo epsilon 2 was associated with a significantly reduced odds ratio for AD above the age of 65 (OR 0.68, 95% CI 0.58-0.80, p < 0.00001), but not in familiar early-onset AD, where apo epsilon 2 may be associated with an increased risk (OR 1.70, 95% CI 1.02-2.84). We estimate that 60% (95% CI 48-68%) of AD cases over the age of 65 years and 92% of cases below the age of 65 would be attributable to apo E and that apo E probably accounts for less than 50% of the familial aggregation of the disease.