Lipid metabolism is involved in the pathogenesis of late-onset Alzheimer's disease (LOAD). Lipoprotein lipase (LPL) is a multifunctional enzyme that plays a major role in lipid metabolism; its abnormal function seems to be related, either directly or indirectly, to the pathogenesis of many diseases such as atherosclerosis, coronary artery disease (CAD) and Alzheimer's disease (AD) . HindIII polymorphism is a common LPL genetic variant shown to increase the risk of LOAD. The present research investigates whether this polymorphism is involved in the pathogenesis of Iranian LOAD patients.In this case control study ,allele and genotype frequencies for the HindIII polymorphism of the LPL gene in 100 patients affected with LOAD and 100 healthy controls were determined by reaction-restriction fragment length polymorphism (PCR-RFLP) and compared using the chi-square and Fisher's exact tests.LPL H+H+ genotype frequency in LOAD patients was 58%, which was significantly higher than controls (44%). There was a 1.75-fold increased risk for the development of LOAD in carriers of the H+H+ genotype compared to non-carriers (OR=1.75; 95%CI: 1.00-3.07; p=0.048). When adjusted for sex, the H+H+ genotype was more frequent in patients than controls; this difference was more remarkable in males (OR: 1.90; 95% CI: 1.08-3.34; p=0.024). The mean age of disease onset did not differ in patients with the LPL H+H+ genotype compared to unaffected individuals.This study confirms the association between the H+H+ genotype with LOAD and supports the correlation of this genotype of the LPL gene with risk of developing LOAD in Iranian patients with AD.