Synaptic calcium dysregulation appears to play an important role in synaptic loss in Alzheimer's disease (AD). Previous studies implicated that the pathological cascade of Alzheimer's disease may be modified by interactions in the amyloid-calcium axis. The calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene encodes the alpha 1C subunit of the L-type voltage-gated calcium channel, which has been suggested to have an important role with the increased amyloid-β load in the plaques. We therefore, examined whether genetic polymorphisms of CACNA1C gene is associated with AD in Korean population by analyzing the genotype and allele frequencies. Additionally, we analyzed the relationship between the genetic polymorphisms of these genes and severity of behavioral and psychological symptoms of dementia (BPSD) based on clinical assessment. The diagnosis of the subjects was based on the ‘National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association’ criteria. AD patients were assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease – Neuropsychological Assessment Battery, The Neuropsychiatric Inventory. Five SNPs, rs216008, rs215976, rs1544514, rs10466907, and rs7957163 in the CACNA1C gene were compared between 278 patients with AD and 195 healthy control subjects using direct sequencing. Multiple logistic regression models were employed to calculate odds ratios (ORs), their 95% confidence intervals (CI) and corresponding p values, controlling for age and gender as covariates. In the logistic regression analysis for each SNP, we compared three different models of gene expression (co-dominant model, dominant model and recessive model). SNP rs10466907 showed significant difference in the allele frequencies between AD and controls (p=0.010). The genotype frequencies of rs10466907 showed significant association between AD and control groups [p=0.003 in the co-dominant model; p=0.01 in the dominant model]. No association was observed between genotype and BPSD severity as measured by the NPI. These results suggest that CACNA1C gene is a promising candidate gene in AD pathogenesis, and may represent a potential predisposing genetic factor for AD.