AbstractAlzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder. To date, apolipoprotein E (apoE) is the only established susceptibility gene for late‐onset AD. ApoE accounts for less than 50% of the risk of AD, indicating the presence of other unknown susceptibility loci. Linkage studies have indicated chromosome 12 as the most likely location for another late‐onset AD locus. We examined seven polymorphisms in five candidate genes located in and around the linkage peaks on chromosome 12 in 564 cases and 523 controls. The genes included complement component 1R (C1R), vitamin D receptor (VDR), scavenger‐receptor B1 (SR‐B1), low‐density lipoprotein receptor related protein 1 (LRP1), and transcription factor LBP‐1c/CP2/LSF. We found no association with C1R, VDR, SR‐B1, and LRP1 polymorphisms. However, the frequency of the A allele of the 3′ (untranslated region) UTR LBP‐1c/CP2/LSF polymorphism was higher in controls than cases (0.071 vs. 0.051; P = 0.042) with an adjusted odds ratio (OR) of 0.65 (95% confidence interval [CI]: 0.43–0.96; P = 0.0498). Our data suggest that the LBP‐1c/CP2/LSF polymorphism may have a moderate protective effect against the risk of AD. © 2003 Wiley‐Liss, Inc.