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Combined risk effects of IDE and NEP gene variants on Alzheimer disease
  1. S Vepsäläinen1,
  2. S Helisalmi1,
  3. A Mannermaa2,
  4. T Pirttilä1,
  5. H Soininen1,
  6. M Hiltunen1
  1. 1
    Department of Neurology, University Hospital and University of Kuopio, Kuopio, Finland
  2. 2
    Department of Pathology and Forensic Medicine, University and University Hospital of Kuopio, Kuopio, Finland
  1. Correspondence to Dr S Vepsäläinen, Department of Neurology, Kuopio University and University Hospital, PO Box 1627, 70211 Kuopio, Finland; saila.vepsalainen{at}


Polymorphisms in genes encoding amyloid β-peptide (Aβ)-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.

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  • Funding Financial support was provided by the Health Research Council of the Academy of Finland, EVO grant 5772708 of Kuopio University Hospital and the Nordic Centre of Excellence of Neurodegeneration.

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the Ethics Committee of the University of Kuopio, Finland.