Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures

Mueller, Jakob C.; Riemenschneider, Matthias; Schoepfer-Wendels, Andreas; Gohlke, Henning; Konta, Lidija; Friedrich, Patricia; Illig, Thomas; Laws, Simon M.; Förstl, Hans; Kurz, Alexander

doi:10.1016/j.neurobiolaging.2006.03.009

« Previous Next »Neurobiology of Aging
Volume 28, Issue 5 , Pages 727-734, May 2007

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures

Jakob C. Mueller
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
- Institute of Medical Statistics and Epidemiology, TUM, Germany
- These two authors contributed equally to this work.
Matthias Riemenschneider
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
- These two authors contributed equally to this work.
- Corresponding author. Tel.: +49 89 4140 4214; fax: +49 89 4140 4888.
Andreas Schoepfer-Wendels
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
Henning Gohlke
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
- Institute of Genetic Epidemiology, GSF, München-Neuherberg, Germany
Lidija Konta
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
Patricia Friedrich
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
Thomas Illig
- Institute of Genetic Epidemiology, GSF, München-Neuherberg, Germany
Simon M. Laws
- Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich (TUM), Ismaningerstr. 22, 81675 München, Germany
Hans Förstl
- Department of Psychiatry and Psychotherapy, TUM, Germany
Alexander Kurz
- Department of Psychiatry and Psychotherapy, TUM, Germany

Received 26 January 2006; received in revised form 21 February 2006; accepted 20 March 2006. published online 04 May 2006.

Abstract

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE).

Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.01). Tests with MMSE scores adjusted for disease duration identified associations, with the most significant result for rs1999763 (nominal p=0.008). Similarly, different reconstructed IDE haplotypes were associated with AD and higher MMSE scores. The association signals are only borderline significant after adjustment for multiple testing, but add further evidence to previous published results on the association between IDE and AD or MMSE. A subgroup analysis indicated more prominent associations with AD in younger, and with MMSE in older patients. There may be two independent effects mediated by IDE variants, risk for AD and modification of disease progression.