Combined risk effects of IDE and NEP gene variants on Alzheimer disease.

Polymorphisms in genes encoding amyloid beta-peptide (A beta)-degrading enzymes neprilysin (NEP) and insulin-degrading enzyme (IDE) individually affect the susceptibility to Alzheimer disease (AD) among the Finnish population. Here we show that a combination of risk genotypes for NEP and IDE genes leads to a higher susceptibility to AD. Individuals with the combination of risk genotypes for NEP and IDE conferred a threefold higher susceptibility to AD when compared with individuals not carrying these genotypes. Although no significant interaction was observed between NEP and IDE genes, these data suggest that NEP and IDE exhibit an additive risk effect in AD.