In well-developed countries with longer life expec­tancy, AD is a major health problem. In 2000, 4.5 million people in the United States were estimated to have AD, the third leading cause of death, after heart disease and cancer [29]. It has been suggested that 22 million people worldwide will develop AD by 2025 [30]. Because of its vast effects on the quality of life for the affected and the caregivers, AD brings heavy demands on health care sys­tems. In the United States, the estimated annual cost of caring for a single AD patient is US$47,000, resulting in a total health care bill of more than US$67.3 billion per year [31-33].

The E4 allele of the ApoE gene is the most common genetic determinant of susceptibility to sporadic AD, which constitutes >98% of all AD cases. The major neuro­pathological phenotype of the E4 genotype is increased amyloid β (Aβ) deposition. ApoE isoforms may affect amyloid levels in the brains of AD patients by being in­volved in the clearance or in the deposition of Aβ. The first would include association of ApoE with Aβ and inter­action between ApoE-Aβ complexes and ApoE receptors [34]. The second is supported by several studies which have suggested that E4 causes greater aggregation of Aβ than does E3 [35].
Significant differences in allelic variations of the ApoE gene have been observed between Caucasian, Chinese, Japanese and Black races [36,37]. The E3 allele is the most common allele in all populations studied, while the E4 allele is not a uniform risk factor for AD in all ethnic groups, including African-Americans and Hispanics [38,39].
The ApoE allele and genotype distributions in 1,017 elderly Turkish individuals are in accordance with those from two previous studies in the Turkish population [24,25]. The frequencies of E2 and E4 alleles are among the lowest reported worldwide and different from those of other Caucasian populations. The low E4 allele agrees with the north-south gradient for the frequency of this allele in Europe (from 24% in Finland to 6.5% in Greece) [40].
The E4 allele is almost twice as frequent in patients with AD, as in non AD controls. Multivariate analyses and OR determinations reveal that carrying at least one E4 allele constitutes a significant risk factor for sporadic AD in the Turkish population. The E2 allele did not lower the risk significantly, although the OR was lower than 1, pos­sibly because of the relatively small population size and low frequency of E2 in this population.
Higher education lowered the risk for AD, but there was no interaction between education level and ApoE status, suggesting that education and ApoE status modify the risk for AD in an independent manner.
In conclusion, the E4 allele of the ApoE gene consti­tutes a significant risk factor for AD in the Turkish popu­lation. The low frequency of the E4 allele may theoreti­cally decrease the probability of developing AD in the Turkish population; this assumption needs to be verified in prevalence studies.

^a Non AD, cognitively normal individuals.