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The BDNF val66met polymorphism is not associated with late onset Alzheimer's disease in three case–control samples

Molecular Psychiatry volume 10, pages 809–810 (2005)Cite this article

SIR—Brain-derived neurotrophic factor (BDNF) has been implicated in hippocampal anatomy and plasticity, learning and memory. BDNF, located on chromosome 11p13, contains a common, functional single nucleotide polymorphism (SNP), rs6265, at codon 66 (val66met) of the pro-region of the protein, which appears to exert an effect on intracellular trafficking and activity-dependent secretion of BDNF.1 Individuals carrying the methionine allele have impaired hippocampal function and volume and poor episodic memory.1 Memory deterioration and hippocampal pathology are prominent features of late-onset Alzheimer's disease (LOAD), and this has prompted several groups to seek association between BDNF polymorphisms and Alzheimer's disease (AD). Association between the val66met polymorphism in BDNF and LOAD was claimed,2 and positive associations of the 270C/T polymorphism, in the 5′-noncoding region of the BDNF gene have also been reported in two different sample sets.3, 4 Other studies have not found evidence for association of either the val66met SNP 5, 6, 7, 8 or the 5′-noncoding 270C/T SNP with AD.8, 9 The studies with lack of association were based on samples of very different ethnic backgrounds including sample sets from Brazil, China, Italy, and Spain. This and the fact that samples of relatively small size were employed in these studies make it difficult to definitively assess the potential association of the BDNF SNPs with LOAD. As a result of its suggested functional significance in AD and other psychiatric disorders such as schizophrenia, bipolar disorder, and anxiety, we chose to genotype the val66met SNP in three independently collected LOAD case control series of Caucasian decent, totaling 2041 individuals (935 cases vs 1106 controls) and examined whether the SNP is associated with LOAD.

The three case–control series were the WU series, collected through the Washington University Alzheimer's Disease Research Center (ADRC) patient registry, the UK series, collected as part of the MRC LOAD Genetic Resource by Cardiff University, Wales College of Medicine and King's College London, and the UCSD series, collected through the ADRC of the University of California, San Diego. Cases in these series have a clinical diagnosis of dementia of the Alzheimer's type according to NINCDS-ADRDA or similar criteria with a minimum age of onset of 65 years. Nondemented controls have a full neuropsychological and clinical interview and are assessed in the same manner as the cases. These samples all show an expected age- and APOE4-genotype distribution and do not appear to have any evidence of population stratification; more detailed information about these samples can be found in our recent publication.10

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Authors and Affiliations

  1. Celera Diagnostics, Alameda, CA, USA

    Y Li, C Rowland, K Tacey, J Catanese, J Sninsky & A Grupe

  2. National Institute on Aging, Bethesda, MD, USA

    J Hardy

  3. Department of Neuroscience, Institute of Psychiatry, King's College, London, UK

    J Powell & S Lovestone

  4. Department of Neurology, Washington University School of Medicine, St Louis, MO, USA

    J C Morris & A Goate

  5. Department of Neuroscience, University of California, San Diego, CA, USA

    L Thal

  6. Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA

    A Goate

  7. Department of Psychological Medicine, Cardiff University, Wales College of Medicine, Cardiff, UK

    M Owen & J Williams

Authors
  1. Y Li
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  2. C Rowland
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  3. K Tacey
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  4. J Catanese
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  5. J Sninsky
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  6. J Hardy
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  7. J Powell
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  8. S Lovestone
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  9. J C Morris
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  10. L Thal
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  11. A Goate
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  12. M Owen
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  13. J Williams
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  14. A Grupe
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Correspondence to A Grupe.

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Li, Y., Rowland, C., Tacey, K. et al. The BDNF val66met polymorphism is not associated with late onset Alzheimer's disease in three case–control samples. Mol Psychiatry 10, 809–810 (2005). https://doi.org/10.1038/sj.mp.4001702

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