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Variation at the APOE −491 promoter locus is associated with altered brain levels of apolipoprotein E

Molecular Psychiatry volume 7, pages 886–890 (2002)Cite this article

Abstract

The apolipoprotein E (APOE, gene; apoE, protein) type 4 isoform is a well-established risk factor for late-onset Alzheimer's disease (AD), and new data suggest that APOE promoter polymorphisms might also modulate AD risk, perhaps by altering transcription of the APOE gene. The current study was undertaken to determine whether the presence of the APOE promoter −491AA genotype (that appears to increase the risk for AD) is associated with an increase in the levels of apoE in brain tissue. Among 40 control and 20 autopsy-confirmed AD brain samples, levels of apoE were increased in the frontal cortex of AD cases (P < 0.001), consistent with the well-recognized up-regulation of APOE expression in reactive astrocytes. Among controls, the −491A allele appeared to impart a gene dose-dependent effect on the levels of apoE in frontal cortex. The levels of apoE in the brains of AD patients with the −491AA genotype were increased as compared to control subjects with the same genotype (P< 0.001). These data support the notion that the −491AA APOE promoter genotype is associated with elevated brain apolipoprotein E levels, suggesting that the risk for AD may be modulated by the apoE protein level as well as by the apoE protein isoform.

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Acknowledgements

This project was supported by the McCusker Foundation for Alzheimer's Disease Research, Hollywood Private Hospital, Department of Veteran Affairs and US NIH Program AG10491. SM Laws is a recipient of a Dora Lush (Biomedical) postgraduate research scholarship from the NHMRC (Australia).

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Authors and Affiliations

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

    S M Laws, E Hone, K Taddei & R N Martins

  2. The Tissue Resource Centre and the Department of Pathology, Neuroscience Institute of Schizophrenia and Allied Disorders, University of Sydney, Blackburn, New South Wales, Australia

    C Harper

  3. The Rebecca L Cooper Research Laboratories, the Mental Health Research Institute of Victoria, University of Melbourne, Parkville, Victoria, Australia

    B Dean

  4. Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia

    C McClean & C Masters

  5. Department of Psychiatry, The University of Western Australia, Perth, Western Australia

    N Lautenschlager

  6. New York University School of Medicine and the Nathan Kline Institute, Orangeburg, New York, USA

    S E Gandy

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  1. S M Laws
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  2. E Hone
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Correspondence to R N Martins.

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Laws, S., Hone, E., Taddei, K. et al. Variation at the APOE −491 promoter locus is associated with altered brain levels of apolipoprotein E. Mol Psychiatry 7, 886–890 (2002). https://doi.org/10.1038/sj.mp.4001097

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  • DOI: https://doi.org/10.1038/sj.mp.4001097

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