Interaction of insulin and PPAR-α genes in Alzheimer's disease: The Epistasis Project

Heike Kölsch*, Donald J. Lehmann, Carla A. Ibrahim-Verbaas, Onofre Combarros, Cornelia M. Van Duijn, Naomi Hammond, Olivia Belbin, Mario Cortina-Borja, Michael G. Lehmann, Yurii S. Aulchenko, Maaike Schuur, Monique Breteler, Gordon K. Wilcock, Kristelle Brown, Patrick G. Kehoe, Rachel Barber, Eliecer Coto, Victoria Alvarez, Panos Deloukas, Ignacio MateoWolfgang Maier, Kevin Morgan, Donald R. Warden, A. David Smith, Reinhard Heun

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Altered glucose metabolism has been described in Alzheimer's disease (AD). We re-investigated the interaction of the insulin (INS) and the peroxisome proliferator-activated receptor alpha (PPARA) genes in AD risk in the Epistasis Project, including 1,757 AD cases and 6,294 controls. Allele frequencies of both SNPs (PPARA L162V, INS intron 0 A/T) differed between Northern Europeans and Northern Spanish. The PPARA 162LL genotype increased AD risk in Northern Europeans (p = 0.04), but not in Northern Spanish (p = 0.2). There was no association of the INS intron 0 TT genotype with AD. We observed an interaction on AD risk between PPARA 162LL and INS intron 0 TT genotypes in Northern Europeans (Synergy factor 2.5, p = 0.016), but not in Northern Spanish. We suggest that dysregulation of glucose metabolism contributes to the development of AD and might be due in part to genetic variations in INS and PPARA and their interaction especially in Northern Europeans.

Original languageEnglish
Pages (from-to)473-479
Number of pages7
JournalJournal of Neural Transmission
Issue number4
Publication statusPublished - Apr 2012

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