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Association between presenilin-1 Glu318Gly mutation and familial Alzheimer's disease in the Australian population

Molecular Psychiatry volume 7, pages 776–781 (2002)Cite this article

Abstract

Mutations in the presenilin-1 (PS-1) gene on chromosome 14 account for the majority of early-onset familial Alzheimer's disease (FAD) cases. To date, more than 90 mutations have been identified and, while most of these mutations are completely penetrant, the Glu318Gly mutation has been suggested to be partially penetrant. These findings indicate that it may play a similar role to apolipoprotein E (APOE)-ε4 by acting as a genetic risk factor for AD. In the current study, a total of 682 subjects were tested to assess the frequency of the Glu318Gly mutation in AD in the Australian population. The Glu318Gly mutation was identified in six sporadic late-onset AD patients, four FAD patients (unrelated) and in nine control subjects. The frequency of this mutation was highest in the familial AD group (8.7%) and lowest in control subjects (2.2%). When the mutation frequencies were compared, we found a statistically significant difference between the latter two groups (Fisher's exact test, P < 0.05). The genotype frequency of the Glu318Gly mutation in all AD cases and controls in the Australian population was 2.8%. This frequency is comparable to that observed for the Dutch population (3.2%), but not for the Finnish population (6.8% and 6.0%) or the Spanish population (5.3%). These findings show that the frequency of the Glu318Gly mutation is increased in FAD patients, suggesting a potential role as a genetic risk factor contributing to the pathogenesis of familial AD.

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Acknowledgements

This work was supported by grants to RNM from Sir James McCusker, Department of Veteran Affairs and the NH&MRC, and by USPHS grant AG10491 to SEG.

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Authors and Affiliations

  1. Department of Surgery, Sir James McCusker Alzheimer's Disease Research Unit and University of Western Australia, Hollywood Private Hospital, Nedlands, Perth, 6009, Australia

    K Taddei, C Fisher, S M Laws, G Martins, A Paton, R M Clarnette & R N Martins

  2. Department of Rehabilitation and Aged Care, Joondalup Health Campus, Joondalup, Perth, 6919, Australia

    C Chung

  3. Centre for Education and Research on Ageing, University of Sydney and Concord Repatriation General Hospital, Concord, 2139, NSW, Australia

    W S Brooks

  4. Department of Psychiatry and Behavioural Science, Stamford University, 94304, California, USA

    J Hallmayer

  5. Division of Neuropathology, University Institute of Pathology, CHUV, Lausanne, 1011, Switzerland

    J Miklossy

  6. Department of Neurology and Neuroscience and the program in Neuroscience, Cornell University Medical College, New York, 10021, USA

    N Relkin

  7. Department of Medicine (Neurology) and Medical Biophysics, University of Toronto and Department of Medicine, Division of Neurology, Centre for Research into Neurodegenerative Diseases, The Toronto Hospital, Toronto, Ontario, M5S3H2, Canada

    P H St George-Hyslop

  8. Alzheimer Research Program, New York University, NS Kline Institute, Orangeburg, New York, 10692, USA

    S E Gandy

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  1. K Taddei
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  2. C Fisher
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  3. S M Laws
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  4. G Martins
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  6. R M Clarnette
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  7. C Chung
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  10. J Miklossy
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  11. N Relkin
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Correspondence to R N Martins.

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Taddei, K., Fisher, C., Laws, S. et al. Association between presenilin-1 Glu318Gly mutation and familial Alzheimer's disease in the Australian population. Mol Psychiatry 7, 776–781 (2002). https://doi.org/10.1038/sj.mp.4001072

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  • DOI: https://doi.org/10.1038/sj.mp.4001072

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