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A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E ε4 allele

Molecular Psychiatry volume 7, pages 782–785 (2002)Cite this article

Abstract

Because of its implication in neuroprotection, formation of long lasting memories and a disturbed function in Alzheimer's disease (AD), brain-derived neurotrophic factor (BDNF) may represent an appropriate candidate gene conferring risk to AD. Recently, a single nucleotide polymorphism (C-270T) within the BDNF gene has been associated with late onset AD in a Japanese population giving an odds ratio (OR) of 3.8. Because of the importance of this finding we analysed the BDNF polymorphism in a German sample consisting of 210 patients with AD and 188 cognitively healthy controls. The T-allele frequency was higher in patients with AD (11.9%) compared to controls (6.9%) (P = 0.035; OR = 2.26; 95% CI: 1.04–4.48). The risk conferred by the T-allele was stronger in patients who lack the ApoE ε4 allele giving an OR of 2.61 (1.21–5.64) P = 0.015, particularly in patients with early onset of the disease; OR 3.13 (1.32–7.43); P= 0.01. Due to the small number of patients showing both, lack of the ApoE ε4 allele and the BDNF T allele (n = 18), the result needs to be confirmed in a larger sample. The results suggest that the BDNF C-270T polymorphism is a relevant risk factor for AD particularly in patients lacking the ApoE ε4 allele in this German sample.

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References

  1. Levi-Montalcini R . The nerve growth factor: thirty-five years later Science 1987; 237: 1154–1162

    Article  CAS  PubMed  Google Scholar 

  2. Barde Y . Trophic factors and neuronal survival Neuron 1989; 2: 1525–1534

    Article  CAS  PubMed  Google Scholar 

  3. Snider W . Functions of the neurotrophins during nervous system development: what the knockouts are teaching us Cell 1994; 77: 627–638

    Article  PubMed  Google Scholar 

  4. Morse J, Wiegand S, Anderson K, You Y, Cai N, Carnahan J et al. Brain-derived neurotrophic factor (BDNF) prevents the degeneration of medial septal cholinergic neurons following fimbria transection J Neurosci 1993; 13: 4146–4156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pringle A, Sundstrom L, Wilde G, Wiliams L, Iannetti F . Brain-derived neurotrophic factor, but not neurotrophin-3, prevents ischaemia-induced neuronal cell death in organotypic rat hippocampal slice cultures Neurosci Lett 1996; 211: 203–206

    Article  CAS  PubMed  Google Scholar 

  6. Hall J, Thomas K, Everitt B . Rapid and selective induction of BDNF expression in the hippocampus during contextual learning Nat Neurosci 2000; 3: 533–535

    Article  CAS  PubMed  Google Scholar 

  7. Linnarsson S, Bjorklund A, Ernfors P . Learning deficit in BDNF mutant mice Eur J Neurosci 1997; 9: 2581–2587

    Article  CAS  PubMed  Google Scholar 

  8. Hof P . Morphology and neurochemical characteristics of the vulnerable neurons in brain aging and Alzheimer's disease Eur Neurol 1997; 37: 71–81

    Article  CAS  PubMed  Google Scholar 

  9. Phillips H, Hains J, Armanini M, Laramee G, Johnson S, Winslow J . BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer's disease Neuron 1991; 7: 695–702

    CAS  PubMed  Google Scholar 

  10. Narisawa-Saito M, Wakabayashi K, Tsuji S, Takahashi H, Nawa H . Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer's disease Neuroreport 1996; 7: 2925–2928

    Article  CAS  PubMed  Google Scholar 

  11. Kang H, Schuman E . Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus Science 1995; 267: 1658–1662

    Article  CAS  PubMed  Google Scholar 

  12. Lindsay R . Neurotrophic growth factors and neurodegenerative diseases: therapeutic potential of the neurotrophins and ciliary neurotrophic factor Neurobiol Aging 1994; 15: 249–251

    Article  CAS  PubMed  Google Scholar 

  13. Kunugi H, Ueki A, Otsuka M, Isse K, Hirasawa H, Kato N et al. A novel polymorphism of the brain derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease Mol Psychiatry 2001; 6: 83–86

    Article  CAS  PubMed  Google Scholar 

  14. Relkin N, Kwon Y, Tsai J, Gandy S . The National Institute on Aging/Alzheimer's Association recommendations on the application of apolipoprotein E genotyping to Alzheimer's disease. In: Relkin N, Khachaturian Z, Gandy S (eds) Apolipoprotein E Genotyping in Alzheimer's Disease Annals of the New York Academy of Sciences: New York 1996; 149–171

    Google Scholar 

  15. McKhann G, Folstein M, Katzman R, Price D, Stadlan EM . Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease Neurology 1984; 34: 939–944

    Article  CAS  PubMed  Google Scholar 

  16. Roth M, Tym E, Mountjoy CQ, Huppert FA, Hendrie H, Verma S et al. CAMDEX. A standardized instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia Br J Psychiatry 1986; 149: 698–709

    Article  CAS  PubMed  Google Scholar 

  17. Welsh KA, Butters N, Mohs RC, Beekly D, Edland S, Fillenbaum G et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery Neurology 1994; 44: 609–614

    Article  CAS  PubMed  Google Scholar 

  18. Folstein MF, Folstein SE, McHugh PR . ‘Mini Mental State’. A practical method for grading the cognitive state of patients for the clinician J Psychiat Res 1975; 12: 189–198

    Article  CAS  PubMed  Google Scholar 

  19. Zivelin A, Rosenberg N, Peretz H, Amit Y, Kornbrot N, Seligsohn U . Improved method for genotyping apolipoprotein E polymorphisms by a PCR-based assay simultaneously utilizing two distinct restriction enzymes Clin Chem 1997; 43: 1657–1659

    CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Neurochemistry and Neurogenetics Laboratory, Technische Universität München (TU-München), Munich, Germany

    M Riemenschneider & S Schwarz

  2. Institute for Medical Statistics and Epidemiology, TU-München, Munich, Germany

    S Wagenpfeil

  3. Department of Human Genetics, Justus Liebig Universität, Giessen, Germany

    U Müller

  4. Department of Psychiatry and Psychotherapy, TU-München, Munich, Germany

    J Diehl, H Förstl & A Kurz

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  1. M Riemenschneider
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  2. S Schwarz
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  4. J Diehl
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  5. U Müller
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  6. H Förstl
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  7. A Kurz
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Correspondence to M Riemenschneider.

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Riemenschneider, M., Schwarz, S., Wagenpfeil, S. et al. A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E ε4 allele. Mol Psychiatry 7, 782–785 (2002). https://doi.org/10.1038/sj.mp.4001073

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