Evaluation of neprilysin sequence variation in relation to CSF β-Amyloid levels and Alzheimer disease risk

Neprilysin (NEP) is a principal peptidase involved in the degradation of β-amyloid (Aβ), and as such its encoding gene (MME) has been the target of numerous genetic association studies on Alzheimer disease. Here, in order to attempt replication of previous findings we have investigated several single nucleotide polymorphisms (SNPs) that have been claimed to be associated with AD. A key feature of the present study is the complementary investigation of both AD risk and quantitative measures of AD severity, including cerebrospinal (CSF) fluid levels of AP1-42. In contrast to the effects of APOE, none of these measures are detectably influenced by genetic polymorphism in the MME region. We thus, fail to find support for previous results suggesting that MME impacts AD.