Objective: The apolipoprotein E (APOE) e4 allele increased the risk for coronary artery disease (CAD), and sporadic and familial late onset Alzheimer's disease (AD). APOE concentration, in addition to APOE polymorphism, might be a risk factor for CAD and cerebrovascular disease (CVD). Interestingly, increased serum APOE levels have been observed in early- and late-onset AD patients compared with controls, supporting the growing evidence that vascular factors play a role in the etiology of AD. Aims of this study were to evaluate the influence of APOE genotype on serum APOE levels, and, secondly, to study serum APOE concentrations in relation to age and Alzheimer’s Disease. Design: APOE genotypes, serum total cholesterol, LDL cholesterol, HDL cholesterol, total cholesterol/HDL cholesterol ratio, triglycerides, and serum APOE were performed on 52 healthy centenarians, 49 AD patients, 45 age-matched controls, and 72 young healthy adults. Materials and Methods: Blood samples were taken after a 13-hours overnight fast; serum APOE concentrations were measured by nephelometry (Nephelometer 100 Analyzer, Behring, Germany). APOE genotypes, TC, TG, LDL-C, and HDL-C were determined as we reported in details elsewhere (Neurosci Lett 1999;277: 53-56; Am J Cardiol 2002;89: 825-829). The statistical analysis was performed by Pearson c2 test (Hardy-Weinberg equilibrium), Cochran-Armitage trend test, and an analysis of covariance on fixed effects factorial design, adding the APOE carriers to the model. The trend in serum APOE levels among the APOE carriers was tested by polynomial orthogonal contrasts. Statistical analyses were performed with BMDP software, version 7.0 (Los Angeles, CA, USA). Results: In all study population a significant trend in reduction of serum APOE levels from APOE e2- to e4-carrier was observed. The difference in serum APOE levels among age groups significantly decreased in e4-carriers only including HDL cholesterol; no significant differences between Alzheimer’s disease patients and age-matched controls were found. Conclusion: The effect of APOE polymorphism on serum APOE level suggests that APOE polymorphism influences primarily APOE-containing lipoproteins, and that this influence is present across all age categories. Significant differences in serum APOE levels respect to age were found in e4-carriers between young healthy adults and age-matched controls, and between young healthy adults and centenarians, but only after adjustment for serum HDL-C levels (in plasma >60% of APOE is associated with HDL). The role of serum APOE concentration in extreme longevity may be explained by the relevance of this factor in CVD and CAD. In these highly selected populations, APOE genotype distribution strongly influences serum APOE concentration, not suggesting, at present, a possible role as a biochemical marker for Alzheimer’s disease, but only as a putative longevity factor.
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