Lack of association of apolipoprotein E allele ϵ4 with late‐onset Alzheimer's disease among Finnish centenarians

Abstract

Article abstract—No association between Alzheimer's disease (AD) and apolipoprotein E type ϵ4 (ApoE ϵ4) phenotype was found among centenarians in Finland (N = 179). The data are based on ascertainment of all centenarians in Finland in 1991. All examinations were conducted during 1991. The diagnoses of dementia and AD were based on clinical grounds, conforming to DSM-III-R and NINCDS-ADRDA criteria. The percentage of ApoE ϵ4 alleles among the centenarians was 8.7% (31 of 358 alleles). This is significantly lower than percentages found in younger Finnish populations. Thirty (16.8%) of the 179 centenarians were ϵ4 allele carriers. One hundred fifty-one (84.4%) of the centenarians were women. Twenty-eight (18.5%) of the women had at least one ϵ4 allele, as did two (7.1%) of the men. The prevalence of clinically diagnosed AD was 26.8%; 44% of the subjects were cognitively normal, 23% had signs of cognitive decline or at most mild dementia (with no differential diagnosis), and 6% had a dementia clinically diagnosed as being due to some cause other than AD. For AD cases versus cognitively normal subjects, the odds ratio associated with being a carrier of the ϵ4 allele was 1.34 (p = 0.64; 95% CI = [0.5, 3.31). Among women, the odds ratio was 0.99 (p = 1.0; 95% CI = [0.4, 2.6]). There were fewer, but not significantly so, ϵ4 carriers among subjects with cognitive decline or at most mild dementia (12.2%) than there were among the cognitively normal subjects (16.5%). Ten (10.4%) of the 96 alleles belonging to AD cases were ϵ4, and 8.9% (14/158) of the alleles belonging to the cognitively normal subjects were ϵ4. This difference is highly nonsignificant. There was only one individual who was homozygous for the ϵ4 allele. She was cognitively normal. Among the 28 men in the study there were only two carriers of the ϵ4 allele; consequently, analyses for men have little power. These results clearly show that the ϵ4 allele does not necessarily lead to AD even near the (current) upper age-limit of life. When combined with previous findings, these results suggest that the association of the ApoE ϵ4 allele with AD may be age-dependent and that the ApoE ϵ4 allele might accelerate the AD dementing process rather than be a direct etiologic agent or a predisposing genetic factor.