Background: Alzheimer’s disease (AD) has a complex genetic etiology, and as a result many genes have been studied to determine how they might be involved with the disease. Amyloidogenic effects have been broadly linked with familial forms of the disease, though certain genes such as UBQLN1 could also play a role in prodromal phases such as amnesic mild cognitive impairment (MCI). Aim: The aim of this study is to examine the role of the UBQ-8i (rs12344615) functional polymorphism in the UBQLN1 gene as a risk factor for MCI and AD and its possible synergies with apolipoprotein gene E (APOE). Material & Methods: 215 MCI patients, 347 sporadic AD sufferers and 238 healthy controls from the Basque Country (Spain) were analysed. Clinical criteria and neuro-psychiatric tests were used to establish the diagnostic groups. SNP, UBQ-8i and the APOE gene were genotyped via real-time polymerase chain reaction (rtPCR), polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLPs) respectively. Multinomial logistic regression models were used to determine the risk for MCI and AD. Results: Allele C of rs12344615 of the UBQLN1 gene is not a risk factor for MCI or AD (OR = 0.88, CI95% 0.60-1.31 p7equal;s0.542 and OR = 0.73, CI95% 0.51-1.02 p=0.079, respectively). Moreover, genotypes with at least one C allele are observed not to show synergies with APOE*E4 in MCI or with AD sufferers. Conclusion: Allele C of polymorphism UBQ-8i of the UBQLN1 gene is not an independent risk factor for MCI or AD. Moreover, this allele is not observed to have any synergy effects with APOE*E4.