Alzheimer disease (AD) is the most frequent cause of dementia, associated with various genetic and non-genetic factors. Apolipoprotein E (ApoE) is a multifunctional protein with central role in the lipid metabolism and neurobiology. ApoE has three common isoforms (e2, e3, e4), encoded by different alleles of a single gene. Among the genetic factors involved in AD susceptibility, the ApoEe4 allele has a major contribution and its presence reduces the age at AD onset.

We aimed to determine the effect of ApoE genotype on the risk of AD in elderly Bulgarians. We genotyped 53 patients with early-onset (EOAD), 58 - with late-onset (LOAD) and 39 gender-, age- and ethnically matched controls individuals. All patients were diagnosed by two referent clinicians according to NINCDS-ADRDA criteria for probable AD. The ApoE genotyping included standard PCR-RFLP analysis followed by polyacrylamide gel electrophoresis and silver staining visualization.

ApoEe3 was the most common allele in the three groups, with significantly higher frequency among the EOAD (87%), than the LOAD patients (72%, p<0.05). In contrast, ApoEe4 allele was significantly more common among the LOAD patients (25%) than in the control (9%, p<0.005) or EOAD (10%, p<0.01) individuals. This allele was found in homo-or heterozygous state in about 50% of AD patients with onset above 65 years of age. There were no gender differences in the ApoE allele distribution. This is the first ApoE association study in Bulgaria. Our data suggest an association of ApoEe4 allele with increased risk of LOAD, but not EOAD in Bulgarian individuals.