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  • Original Article
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Genome scan on Swedish Alzheimer's disease families

Molecular Psychiatry volume 11, pages 182–186 (2006)Cite this article

Abstract

Alzheimer's disease (AD) is an age-related disease, which affects approximately 40% of the population at an age above 90 years. The heritability is estimated to be greater than 60% and there are rare autosomal dominant forms indicating a significant genetic influence on the disease process. Despite the successes in the early 1990s when four genes were identified, which directly cause the disease (APP, PSEN1 and PSEN2) or greatly increase the risk of disease development (APOE), it has proved exceedingly difficult to identify additional genes involved in the pathogenesis. However, several linkage and association studies have repeatedly supported the presence of susceptibility genes on chromosomes (chrms) 9, 10 and 12. The study populations have, however, mostly been of great genetic heterogeneity, and this may have contributed to the meagre successes in identifying the disease associated genetic variants. In this study, we have performed a genome wide linkage study on 71 AD families from the relatively genetically homogeneous Swedish population where it is also possible to study the genetic ancestry in public databases. We have performed nonparametric linkage analyses in the total family material as well as stratified the families with respect to the presence or absence of APOE ɛ4. Our results suggest that the families included in this study are tightly linked to the APOE region, but do not show evidence of linkage to the previously reported linkages on chrms 9, 10 and 12. Instead, we observed the next highest LOD score on chromosome 5q35 in the total material. Further, the data suggest that the major fraction of families linked to this region is APOE ɛ4 positive.

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Acknowledgements

We thank Sumitomo Pharmaceuticals for generous support throughout the study. We thank Dr Ingrid Kockum at Department of Molecular Medicine, CMM, Karolinska Institutet, Sweden for guidance in using the Allegro Programme, Associate Professors Nenad Bogdanovic and Inger Nennesmo for the neuropathology and Drs Anders Sandström at Sunderby Hospital, Luleå, Börje Lind at Gävle Hospital, Gävle and Stellan Båtsman at Kalix Primary Care Health, Kalix for referring new families to the study, Kurt Johansson and Lars Lannfelt for clinical examinations at Karolinska University Hospital, Huddinge, Sweden. We also wish to thank all the participating families without whom the study could not be performed.

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Authors and Affiliations

  1. Department Neurotec, Karolinska Institutet Sumitomo Pharmaceuticals Alzheimer Center (KASPAC), Karolinska Institutet, Novum, Huddinge, Sweden

    A Sillén, C Forsell, L Lilius, K Axelman, B Winblad & C Graff

  2. Department Neurotec, Experimental Geriatrics, Novum, Karolinska University Hospital Huddinge, Huddinge, Sweden

    B F Björk

  3. Department of Biosciences at Novum, Centre for Biotechnology, Karolinska University Hospital Huddinge, Huddinge, Sweden

    P Onkamo & J Kere

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  1. A Sillén
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Correspondence to C Graff.

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Sillén, A., Forsell, C., Lilius, L. et al. Genome scan on Swedish Alzheimer's disease families. Mol Psychiatry 11, 182–186 (2006). https://doi.org/10.1038/sj.mp.4001772

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