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Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease

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Abstract.

We recently reported that a linkage disequilibrium (LD) block on chromosome 10q encompassing the gene encoding insulin-degrading enzyme (IDE) harbors sequence variants that associate with Alzheimer disease (AD). Evidence also indicated effects upon a number of quantitative indices of AD severity, including age-at-onset (AAO). Since linkage of this immediate region to AAO has been shown in both AD and Parkinson disease (PD), we have explored the possibility that polymorphism within this LD block might also influence PD. Utilizing single nucleotide polymorphisms that delineate common haplotypes from this region, we observed significant evidence of association with AAO in an Australian PD case-control sample. Analyses were complemented with AAO data from two independent Swedish AD case samples, for which previously reported findings were replicated. Results were consistent between AD and PD, suggesting the presence of equivalent detrimental and protective alleles. These data highlight a genomic region in the proximity of IDE that may contribute to AD and PD in a similar manner.

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Acknowledgements.

Financial support was provided by Pfizer, NIA grant no. R01_AG08724, The Swedish Medical Research Council, Loo and Hans Ostermans Foundation, The Swedish Old Servants Foundation (Gamla Tjänarinnor), Åke Wibergs Foundation, Torsten and Ragnar Söderbergs Foundation, Fredrik and Ingrid Thurings Foundation, and The Swedish Alzheimer Foundation (Alzheimerfonden). G.M. and D.B. are supported by the Geriatric Medical Foundation of Queensland. This study was approved by the Princess Alexandra Hospital, University of Queensland and Karolinska Institute research ethics committees.

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Authors and Affiliations

  1. Center for Genomics and Bioinformatics, Karolinska Institute, Stockholm, Sweden

    Mia E.-L. Blomqvist, Anthony J. Brookes & Jonathan A. Prince

  2. Department of Neurology, University of Queensland School of Medicine, Princess Alexandra Hospital, Brisbane, Australia

    Peter A. Silburn, Daniel D. Buchanan & George D. Mellick

  3. Neurotec, Department of Geriatric Medicine, Huddinge University Hospital, Stockholm, Sweden

    Niels Andreasen

  4. Department of Clinical Neuroscience and Transfusion Medicine, University of Göteborg, Sahlgren’s University Hospital, Gothenburg, Sweden

    Kaj Blennow

  5. Department of Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden

    Nancy L. Pedersen

  6. Center for Genomics and Bioinformatics, Karolinska Institute, Berzeliusvag 35, 171 77 Stockholm, Sweden

    Jonathan A. Prince

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  1. Mia E.-L. Blomqvist
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  2. Peter A. Silburn
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Correspondence to Jonathan A. Prince.

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Blomqvist, M.EL., Silburn, P.A., Buchanan, D.D. et al. Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease. Neurogenetics 5, 115–119 (2004). https://doi.org/10.1007/s10048-004-0173-4

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  • DOI: https://doi.org/10.1007/s10048-004-0173-4

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