Apolipoprotein E type ε4 allele, heritability and age at onset in twins with Alzheimer disease and vascular dementia

Abstract

The apolipoprotein E (APOE) ε4 allele is a risk factor in Alzheimer disease (AD), but not in vascular dementia (VaD). We have investigated whether the ε4 allele is more common in twin pairs concordant for AD, compared with those discordant for AD, and whether the ε4 allele is more common in AD twins than in VaD twins. In addition, we have investigated the relationship of the ε4 allele and the age at onset in AD and VaD. APOE genotype was analysed in 29 senile demented twin pairs. The ε4 allele was associated with AD and not with VaD. However, there was no difference in the frequency of the APOE ε4 allele in concordant (33.3%) and discordant (31.3%) AD dizygotic twin pairs. Age at onset in AD was significantly lower in ε4 homozygotes than in individuals with one or no copies of ε4 (62.4 vs. 73.5, p < 0.01). In concordant AD twin pairs, the ε4 allele frequency was somewhat higher in the twins with earlier onset (41.7% vs. 25%), but the difference was not statistically significant. In the VaD group the age at onset was not significantly different between individuals with or without ε4 in their genotypes.

Interaction of Apolipoprotein E Genotypes, Lifestyle Factors and Future Risk of Dementia-Related Mortality: The Cohort of Norway (CONOR)

“…The ApoE allele frequencies among our living controls (8.0, 75.6 and 16.4% for ε2, ε3 and ε4, respectively) were similar to those reported from healthy controls in a recent Norwegian study (10.6, 75.0 and 14.4%) [29] and in a Norwegian study of elderly participants (9.0, 72.8 and 18.2%) [30]. Furthermore, our frequencies are similar to those reported in the Norwegian twin study of AD and vascular dementia where all the cases were clinically diagnosed [31]; the allele frequencies in nondemented twins were 9.1, 68.2 and 22.7% for ε2, ε3 and ε4, respectively, and for AD-verified cases the distribution was 3.6, 60.7 and 35.7%. Thus, our sample seems to be representative of the Norwegian population regarding ApoE allele frequencies.…”

“…The ApoE allele frequencies in our sample from a general population resemble those reported in previous Nordic [28] and Norwegian studies [29,30,31]. The ApoE allele frequencies among our living controls (8.0, 75.6 and 16.4% for ε2, ε3 and ε4, respectively) were similar to those reported from healthy controls in a recent Norwegian study (10.6, 75.0 and 14.4%) [29] and in a Norwegian study of elderly participants (9.0, 72.8 and 18.2%) [30].…”

Genetics of Alzheimer's Disease: A Centennial Review

“…Given that the ApoE status was not determined or inferred for the AD relatives in this study, and the small numbers of non-ε4 positive concordant twins, it is not possible to accurately estimate the contribution of genes other than ApoE for development of AD in first degree relatives of AD twins. Bergem and Lannfelt [ 27 ] determined that in a collection of Norwegian twin pairs, the frequency of the ApoE ε4 allele did not differ between concordant and discordant dizygotic twin pairs, though the presence of this allele was associated with an earlier age at onset. These findings from twin studies suggest that while ApoE accounts for risk and earlier age at onset of AD (the two phenotypes are interdependent for late-onset diseases), this gene does not explain all of the genetic risk for AD.…”

Genome-wide Association Studies in Alzheimer’s Disease: A Review

“…5, 6 Families multiply affected by LOAD are at increased risk for dementia, but the distribution of secondary cases is not consistent with Mendelian inheritance. LOAD is more frequent among monozygotic than dizygotic twins, 7–9 and first-degree relatives of patients with LOAD have approximately twice the expected lifetime risk of developing the disease. Heritabilities of 58% to 79% for LOAD indicate that in spite of progress made in identifying the underpinnings of the disease, a substantial fraction of LOAD is attributable to unknown genetic factors.…”