The transcription factor LBP-1c/CP2/LSF (LBP-1c) is a candidate gene for Alzheimer's disease (AD) because it is located in a putative hotspot for an AD risk gene on chromosome 12. We investigated the effect of LBP-1c polymorphism on the risk of AD in 162 AD patients, 180 patients with major depression as hospitalized controls and 225 healthy subjects. We observed no significant association of the LBP-1c A allele with AD. Nor did we detect an interaction of the LBP-1c A allele with the apolipoprotein E4 (ApoE4) allele or the low-density lipoprotein receptor-related protein T allele which could have been related to the risk of AD. However, exploratory data analysis revealed that the LBP-1c A allele might act as a protective factor in major depression. A recent study also described an association of another gene located on chromosome 12, the mannose 6-phosphatase receptor gene, with major depression. These data suggest the presence of a putative risk gene for major depression at chromosome 12.