The objective of the study was to analyze the frequency of APOE4 allele in elderly patients with Alzheimer’s or vascular dementia or depression; compare these to age/sex matched controls; compare the results with established literature and highlight new findings. A single center, multiple disease, case-control study was performed with three case groups- probable AD patients (n=36), vascular dementia patients (n=29) and depression patients (n=20) and with a control group (n=32). APOE genotyping was performed in whole blood samples collected from patients and controls by restriction isotyping using the enzymes AflIII and HaeII. There was significant difference in frequency distribution of E4 allele between the AD (12/72; 16.7%) and control groups (3/64; 4.7%) (P=0.03). However, no significant difference was found in any of the other comparisons. The current study demonstrates absence of a significant association between APOE4 positivity and presence of late-onset depression in the north Indian elderly and reinforces the higher APOE4 prevalence in LOAD patients but not in VD patients. It is the first study of its kind from the northern part of India involving multiple disease groups and lays the framework for larger cohort studies.