Original Article Evaluation of Neprilysin sequence variation in relation to CSF β-Amyloid Levels and Alzheimer disease risk
Mia E. Blomqvist, Shane McCarthy, Kaj Blennow, Björn Andersson, Jonathan A. Prince
Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden; Sebat Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA; Department of Clinical Neuroscience and Transfusion Medicine, University of Göteborg, Sahlgren's University Hospital, Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden
Received July 20, 2009; accepted July, 2009; available online July, 2009
Abstract: 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 Aβ1-42. 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. (IJMEG907002).
Address all correspondence to: Dr. Jonathan A. Prince Department of Cell and Molecular Biology Karolinska Institute Berzelius väg 35 S-171 77 Stockholm, Sweden Phone: +46 (0)8 5248 6274 Fax: +46 (0)8 324 826 E-mail: Jonathan.Prince@ ki.se