There is evidence consistent with the hypothesis that genetic, inflammatory and immune mechanisms are involved in the pathogenesis of AD. The aim of this study is to assess the relationship between Apolipoprotein E (Apo E), serum levels of inflammatory markers, and cognitive functions among elderly patients with Alzheimer’s disease (AD) and Mild cognitive impairment (MCI) compared to elderly with normal cognitive function. 88 participants (≥60 years) from Ain Shams University Hospital were enrolled. They were divided into 3 groups: Group A (32 elderly patients with AD), Group B (32 elderly patients with MCI) and Group C (24 controls with normal cognitive function). All participants were subjected to comprehensive geriatric assessment, Apo E genotyping, measurement of C-reactive protein (CRP) and Alpha-1-antichymotrypsin (ACT), by PCR-RFLP, ELIZA and semi-quantitative method respectively. The most common variant of Apo E gene was E3/E3 being more frequent in healthy control group (HC) than the other two groups and the least common variant was E4/E4 detected only in the AD group. ApoE4 allele was associated with 40.6% of AD patients (where 31.4% were heterozygous and 8.6 % homozygous) and 17.1% of MCI patients, whereas ApoE2 was more prevalent in the control group (P<0.05). A significant difference was observed when Mini mental status Examination (MMSE) score in different Apo E alleles was compared (P<0.01). The highest score was associated with (E2/E3) allele whereas, the lowest score was associated with (E4/E4) allele. Regarding inflammatory markers; CRP levels showed a statistically significant difference between the 3 groups and were higher in the AD group than the other 2 groups. (P<0.01). There was no statistically significant difference between the 3 groups as regard ACT level (P>0.05). Carriers of at least one E4 allele showed great risk to develop AD when combined with high CRP serum levels (OR = 36; CI: 11.4-113.7; P< 0.01). In conclusion, Apo E together with CRP may be a useful tool to predict Alzheimer’s disease.