In this study, we investigate the impact of apolipoprotein E epsilon 4 (APOE ε4) as a major risk factor of Alzheimer’s disease (AD), based on the clinical presentation of the disease in our population on the one hand, and comparison of the results with the findings from the literature on the other hand. Our study covered a population of 144 patients versus 90 healthy controls matched with each other in terms of age, gender, age of onset, etc. All patients underwent neurological examination, comprehensive neuropsychological assessmentand brain magnetic resonance imaging. Controls were selected based on the neurological examination and the Arabic version of the minimental state examination (MMSE). Patients were classified as probable typical amnestic AD and atypical nonamnestic AD if the patient had logopenic variant primary aphasia, posterior cortical atrophy, behavioural or dysexecutive variants, corticobasal syndrome, nonfluent and semantic variants of primary progressive aphasia associated to biological diagnosis for AB42, Tau and Ptau biomarks in the cerebrospinal fluid. Genotyping was performed using the polymerace chain reaction restriction fragment length polymorphism (PCR-RFLP) method. Thestudy of the allelic frequency of APOE in cases and controls show that APOE ε4 is associated with an increased risk for AD (P = 0.002). We observed that the distribution of APOE ε4 within the AD group differs depending on the phenotype. Nonamnestic AD was more common in patients not carrying APOE ε4 (APOE ε4 (-)) compared to carriers of homozygous or heterozygous APOE ε4 (APOE ε4 (+)) (P = 0.038). In addition to its known effect as a major risk factor, we found that patients with AD are APOE ε4 negative, they show cognitive decline in nonmemory domains (language, behaviour, attention, executive and visuospatial functions).