The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease

Although the epsilon 4 allele of the apolipoprotein E gene appears as an im portant biological marker for Alzheimer's disease (AD) susceptibility, othe r genetic determinants are clearly implicated in the AD process. Here, we p ropose that a genetic variation in the transcriptional factor LBP-1c/CP2/LS F gene, located close to the LRP locus, is a genetic susceptibility factor for AD. We report an association between a non-coding polymorphism (G-->A) in the 3'-untranslated region elf this gene and sporadic AD in French and B ritish populations and a similar trend in a North American population. The combined analysis of these three independent populations provides evidence of a protective effect of the A allele (OR = 0.58, 95% CI 0.44-0.75). We de scribe a potential biologically relevant role for the A allele whereby it r educes binding to nuclear protein(s). The absence of the A allele was assoc iated with a lower LBP-1c/CP2/LSF gene expression in lymphocytes from AD ca ses compared with controls. Our data suggest that polymorphic variation in the implication of the LBP-1c/CP2/LSF gene may be important for the pathoge nesis of AD, particularly since LBP-1c/CP2/LSF interacts with proteins such as GSK beta, Fe65 and certain factors involved in the inflammatory respons e.