The deposition of amyloid beta peptide (Abeta) in the form of plaques in the brain is a hallmark of Alzheimer's disease (AD). Neprilysin is the major Abeta-degradating enzyme and reduction in neprilysin activity could contribute to Alzheimer's by increasing the steady-state level of Abeta. To provide further evidence for the role of neprilysin in AD we genotyped 22 polymorphisms, 21 SNPs and the GT repeat in the promoter region, across the neprilysin gene in 298 Caucasian sporadic Alzheimer's patients and 298 age-matched controls. Several SNPs showed genotypic and allelic association to AD. SNP rs1836915, in linkage disequilibrium block 2, showed the greatest extent of genotypic association with AD (p=0.0076). We were unable to replicate any of the SNPs that were previously reported as putatively associated with AD. However, these novel findings add to the weight of evidence supporting the involvement of neprilysin in the aetiology of Alzheimer's disease.