J Neurol Neurosurg Psychiatry 75:1746-1748 doi:10.1136/jnnp.2004.036574
  • Short report

Polymorphisms in neprilysin gene affect the risk of Alzheimer’s disease in Finnish patients

  1. S Helisalmi1,2,
  2. M Hiltunen1,2,
  3. S Vepsäläinen1,2,
  4. S Iivonen1,2,
  5. A Mannermaa3,
  6. M Lehtovirta1,4,
  7. A M Koivisto1,2,
  8. I Alafuzoff1,3,
  9. H Soininen1,2
  1. 1Department of Neuroscience and Neurology, University Hospital and University of Kuopio, Kuopio, Finland
  2. 2Brain Research Unit, Clinical Research Centre/Mediteknia, University of Kuopio, Kuopio, Finland
  3. 3Department of Pathology and Forensic Medicine, University Hospital and University of Kuopio, Kuopio, Finland
  4. 4Department of Neurology, Jorvi Hospital, Espoo, Finland
  1. Correspondence to:
 S Helisalmi PhD
 Brain Research Unit, Clinical Research Centre/Mediteknia, Department of Neuroscience and Neurology, Kuopio University, Harjulantie 1, PO Box 1627, 70211 Kuopio, Finland;
  • Received 14 January 2004
  • Accepted 1 March 2004
  • Revised 19 February 2004


Objectives: Neprilysin (NEP) is an amyloid β-peptide (Aβ) degrading enzyme expressed in the brain, and accumulation of Aβ is the neuropathological hallmark in Alzheimer’s disease (AD). In this study we investigated whether polymorphisms in the NEP gene have an effect on the risk for AD.

Methods: The frequencies of seven single nucleotide polymorphisms (SNPs) and apolipoprotein E (APOE) were assessed in 390 AD patients and 468 cognitively healthy controls. Genotypes of the study groups were compared using binary logistic regression analysis. Haplotype frequencies of the SNPs were estimated from genotype data.

Results: Two SNPs, rs989692 and rs3736187, had significantly different allelic and genotypic frequencies (uncorrected p = 0.01) between the AD and the control subjects and haplotype analysis showed significant association between AD and NEP polymorphisms.

Conclusion: Taken together, these findings suggest that polymorphisms in the NEP gene increase risk for AD and support a potential role for NEP in AD.


  • This study was supported by the Health Research Council of the Academy of Finland, EVO grants (5772708) of Kuopio University Hospital, and European Union 5th Framework programme (QLK-6-CT-1999-02112).

  • Competing interests: none declared

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