| Summary: | Background: the apolipoprotein e4 allele (<i>APOE4</i>) constitutes an established genetic risk factor for Alzheimer’s Disease Dementia (ADD). We aimed to explore the frequency of the <i>APOE</i> isoforms in the Greek population of Southern Greece. Methods: peripheral blood from 175 Greek AD patients, 113 with mild cognitive impairment (MCI), and 75 healthy individuals. DNA isolation was performed with a High Pure PCR Template Kit (Roche), followed by amplification with a real-time qPCR kit (TIB MolBiol) in Roche’s Light Cycler PCR platform. Results: <i>APOE4</i> allele frequency was 20.57% in the ADD group, 17.69% in the MCI group, and 6.67% in the control group. <i>APOE3/3</i> homozygosity was the most common genotype, while the frequency of <i>APOE4/4</i> homozygosity was higher in the AD group (8.60%). <i>APOE4</i> carrier status was associated with higher odds for ADD and MCI (OR: 4.49, 95% CI: [1.90–10.61] and OR: 3.82, 95% CI: [1.59–9.17], respectively). Conclusion: this study examines the <i>APOE</i> isoforms and is the first to report a higher <i>APOE</i> frequency in MCI compared with healthy controls in southern Greece. Importantly, we report the occurrence of the <i>APOE4</i> allele, related to ADD, as amongst the lowest globally reported, even within the nation, thus enhancing the theory of ethnicity and latitude contribution.
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