Exclusion of CYP46 and APOM as candidate genes for Alzheimer's disease in a French population.

Alzheimer's disease (AD) is a complex, multifactorial disorder, probably resulting from an interaction between environmental and genetic factors. Increasing evidence points to a link between cholesterol turnover and AD, suggesting that genes implicated in brain cholesterol homeostasis may be potential candidate genes for AD. With this background, we tested the potential association of the CYP46, APOM and APOF genes with the risk of developing AD. CYP46 encodes the enzyme cholesterol 24-hydrolase, which plays a key role in brain cholesterol turnover, and APOF and APOM encode apolipoproteins belonging to the large lipocalin family, which also includes ApoE. In contrast to two previous reports but in accordance with one other, we were unable to detect an association between an intron 2 polymorphism of CYP46 and AD. We also searched for polymorphisms within the APOM and APOF by dHPLC. We were unable to detect any polymorphisms in the coding and exon/intron sequences of the APOF. Finally, we excluded APOM as a genetic determinant of AD in our large French case control population.