The human ApoE gene (OMIM #107741) is located in a cluster with ApoC-I, ApoC-I' and ApoC-II on the long arm of chromosome 19. It contains four exons and spans 3.7 kb [4]. Thus, the transcription start site lies in the second exon and the first exon is not translated. Some 30 ApoE variants have been characterized, of which 14 are associated with familial dysbetalipoproteinemia [5]. The most common variants are ApoE2, ApoE3 and ApoE4, with frequencies of 0.11, 0.72 and 0.17, respectively [6]. The E4 isoform is associated with increased levels of total cholesterol and betalipoprotein [7] that result in an in­creased susceptibility to heart disease [8]. Because of its reduced binding affinity to cellular receptors, the E2 iso­form is associated with decreased levels of cholesterol and betalipoprotein [7]. Most of type II hyperlipidemia pa­tients are homozygous for E2 [9].

The ApoE protein (ApoE) is a major serum lipoprotein of 34.2 kDa, that is secreted by many organs, such as mac­rophages, adrenal glands, and mainly by the liver [10]. It is incorporated into lipoproteins and directs their catabo­lism via binding receptors [11]. Although ApoE cannot cross the blood-brain barrier, it is present in the cerebro­spinal fluid as a component of lipoproteins and lipid com­plexes and is the main apolipoprotein in the brain, synthe­sized by astrocytes [12]. It is thought to be involved in the metabolism and redistribution of cholesterol and phospho­lipid during membrane modelling, by its ability to bind and transport cholesterol-rich lipids into cells via interac­tion with ApoE receptors. The increased synthesis of ApoE after neuronal injury, in peripheral and central nervous systems, indicates its involvement in neuronal regenera­tion [13]. There is also an isoform-specific effect of ApoE on the growth and sprouting of cultured dorsal root ganglia neurons and on a murine neuroblastoma cell line [14].

The E4 allele is associated with sporadic and familial AD of early- or late-onset [15], Lewy body dementia [16], severe cerebral amyloid angiopathy [17], and Creutzfeldt-Jakob disease [18]. It may influence the preclinical pro­gression, and therefore the age of onset. Increased fre­quency of the E4 allele was first observed in late-onset familial AD, but further studies demonstrated that it was also overrepresented in sporadic LOAD cases and in young-onset cases in which there was approximately 3-fold higher frequency [19-21]. The decrease in frequency of E2 allele in AD suggests that it has a negative or pro­tective effect on AD [22]. These results have been con­firmed in several populations [23].

The distribution of the ApoE allele frequency in two groups of the adult Turkish population (mean ages 40.8 and 44.3 years, respectively) has been reported previously [24,25]. The objective of the present study is to determine the frequency of the common ApoE alleles, E2, E3 and E4, in a Turkish population with AD, and in non-AD el­derly controls, in order to determine the risk constituted by ApoE allele status for AD.