Table 3 shows the genotype/allele distributions of the ApoE gene and results of binary logistic regression in the Italian cohort. Significant P-values and associations are in bold. The results indicate that the 4-allele was negatively associated with the likelihood of becoming a centenarian in all three cohorts. A novel finding of this study was that the 2-allele seems to specifically favor EL in the Italian and Japanese population, although this result was not corroborated in the Spanish cohort. Of note, the 2-allele might also specifically favor successful or healthy EL in the Italian cohort studied. This allele was more frequent in Italian centenarians who were free of dementia or any other major age-related condition compared with their young controls, and was also more frequent in the oldest Italian centenarians than in the rest of this group.

Table 4 shows subgroup comparisons of genotype/allele distributions of the ApoE gene and results of binary logistic regression in Italian centenarians. Significant P-values and associations are in bold. The results indicate that the 4-allele is negatively associated with EL, a finding which was corroborated in all three independent cohorts.

There are large differences in ApoE allele frequencies among geographical areas and populations, e.g., with high relative frequencies of ApoE4 in Northern Europe (15-21%), intermediate frequencies in Central Europe (11-13%), and low frequencies in Southern Europe (4-6%). The 4-allele frequency in the Spanish (10%) and Italian (8%) young controls was relatively higher than that previously reported by Lewis and Brunner (2004) in Southern Europe. Whereas, the ApoE 4-allele frequency in Spanish and Italian centenarians was 4.9% and 3.2% respectively, which is within the range of previously published frequencies (1-10%) for European centenarians.

Table 5 shows the genotype/allele distributions of the ApoE gene and results of binary logistic regression in the Japanese cohort. Significant P-values and associations are in bold. The results indicate that the 4-allele was negatively associated with EL in all three cohorts. 

Table 6 shows subgroup comparisons of genotype/allele distributions of the ApoE gene and results of binary logistic regression in Japanese centenarians. There were no significant P-values or associations found.

Several biological mechanisms postulate ApoE, particularly the 4-allele, as a candidate to influence longevity. The view that ApoE is more of a frailty or disease-risk gene than a longevity gene has been debated, with its effects on death theoretically decreasing at very old ages. However, our results seem to support previous data on Scandinavian twins showing an increasing mortality risk associated with the ApoE 4-allele with advancing age or those showing lower frequency of this allele in centenarians compared with younger controls of various ethnicities. Our data seem to be in agreement with another hypothesis, the multifactorial threshold model, according to which many single factors each with a small yet significant effect add up and contribute to a disorder/condition (or death) to happen with age.The text appears to be a mix of statistical data and scientific research on the association between ApoE polymorphisms and age-related conditions like CVD and AD. The writer has used some abbreviations like 95% CI for 95% confidence interval and OR for odds ratio. There are also some grammatical errors and typos that need to be corrected. Here's the processed text:

Abbreviations: 95% CI, 95% confidence interval; OR, odds ratio (adjusted for sex). The 4-allele is a well-established risk factor for age-related conditions, mainly CVD and AD. A meta-analysis of 121 studies showed that this allele is associated with higher CVD risk, coupled with higher plasma cholesterol levels (Bennet et al., 2007). The association with CVD may be due to higher LDL cholesterol and triglyceride levels in the plasma of 4-carriers (Dallongeville et al., 1992). A recent meta-analysis of 21 studies on ApoE polymorphisms and AD concluded that the 4-allele is strongly associated with a significantly higher risk of sporadic late-onset AD (Sadigh-Eteghad et al., 2012). ApoE-lipoproteins bind to several cell-surface receptors to deliver lipids and also to hydrophobic amyloid-(A) peptide, which is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD (Liu et al., 2013). ApoE isoforms differentially regulate A aggregation and clearance in the brain and have important functions in regulating brain lipid transport, glucose metabolism, neuronal signaling, neuroinflammation, and mitochondrial function (Liu et al., 2013), with the 4-allele being associated with higher A cellular uptake, leading to more A aggregation compared to 3 (Liu et al., 2013; Smith 2002; Verghese et al., 2013). The aggregation of A is linked to the loss of dendritic spines and accelerating memory impairments in AD (Hashimoto et al., 2012; Wu et al., 2010). A recent study showed that the levels of A oligomers in AD patients were lowest in those carrying the 2-allele (Hashimoto et al., 2012). The 2-allele also seems to play a protective role against CVD (Bennet et al., 2007; Gerdes et al., 2000; Kolovou et al., 2002), although the evidence is probably weaker than for the negative effect of the 4-allele (Drenos and Kirkwood, 2010). In addition, previous large population-based longitudinal studies, i.e., the Rotterdam study (Slooter et al., 2001) and the Danish 1905 birth cohort (Lindahl-Jacobsen et al., 2013), reported no favorable effect of the 2-allele on mortality in the elderly, despite protecting against cognitive decline in the oldest old (93 years) (Lindahl-Jacobsen et al., 2013).