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BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF.

Abstract

BACKGROUND

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months.

METHODS

Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+.

RESULTS

At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF.

CONCLUSION

While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD.

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  • Authors+Show Affiliations

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    The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia.

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    Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia.

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    School of Pharmacy and Medical Sciences,University of South Australia,Adelaide,South Australia,Australia.

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    Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia.

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    Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia.

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    Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia.

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    Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship,Australian e-Health Research Centre-BiaMedIA,Brisbane,Queensland,Australia.

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    Academic Unit for Psychiatry of Old Age,St. Vincent's Health,The University of Melbourne,Kew,Victoria,Australia.

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    The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia.

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    Commonwealth Scientific Industrial Research Organization (CSIRO) Preventative Health National Research Flagship,Australian e-Health Research Centre-BiaMedIA,Brisbane,Queensland,Australia.

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    The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia.

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    Department of Nuclear Medicine and Centre for PET,Austin Health,Heidelberg,Victoria,Australia.

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    The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia.

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    School of Pharmacy and Medical Sciences,University of South Australia,Adelaide,South Australia,Australia.

    ,

    Centre of Excellence for Alzheimer's Disease Research and Care,Edith Cowan University,Joondalup,Western Australia,Australia.

    The Florey Institute,The University of Melbourne,Parkville,Victoria,Australia.

    Source

    International psychogeriatrics 29:11 2017 11 pg 1825-1834

    MeSH

    Aged
    Aged, 80 and over
    Alzheimer Disease
    Brain-Derived Neurotrophic Factor
    Female
    Genotype
    Hippocampus
    Humans
    Male
    Memory, Episodic
    Middle Aged
    Neuroimaging
    Neuropsychological Tests
    Polymorphism, Genetic
    Positron-Emission Tomography

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28720165

    Citation

    Lim, Yen Ying, et al. "BDNF Val66Met in Preclinical Alzheimer's Disease Is Associated With Short-term Changes in Episodic Memory and Hippocampal Volume but Not Serum MBDNF." International Psychogeriatrics, vol. 29, no. 11, 2017, pp. 1825-1834.
    Lim YY, Rainey-Smith S, Lim Y, et al. BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF. Int Psychogeriatr. 2017;29(11):1825-1834.
    Lim, Y. Y., Rainey-Smith, S., Lim, Y., Laws, S. M., Gupta, V., Porter, T., ... Maruff, P. (2017). BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF. International Psychogeriatrics, 29(11), pp. 1825-1834. doi:10.1017/S1041610217001284.
    Lim YY, et al. BDNF Val66Met in Preclinical Alzheimer's Disease Is Associated With Short-term Changes in Episodic Memory and Hippocampal Volume but Not Serum MBDNF. Int Psychogeriatr. 2017;29(11):1825-1834. PubMed PMID: 28720165.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF. AU - Lim,Yen Ying, AU - Rainey-Smith,Stephanie, AU - Lim,Yoon, AU - Laws,Simon M, AU - Gupta,Veer, AU - Porter,Tenielle, AU - Bourgeat,Pierrick, AU - Ames,David, AU - Fowler,Christopher, AU - Salvado,Olivier, AU - Villemagne,Victor L, AU - Rowe,Christopher C, AU - Masters,Colin L, AU - Zhou,Xin Fu, AU - Martins,Ralph N, AU - Maruff,Paul, Y1 - 2017/07/19/ PY - 2017/7/20/pubmed PY - 2018/6/13/medline PY - 2017/7/20/entrez KW - Alzheimer's disease KW - brain-derived neurotrophic factor KW - hippocampal volume KW - memory SP - 1825 EP - 1834 JF - International psychogeriatrics JO - Int Psychogeriatr VL - 29 IS - 11 N2 - BACKGROUND: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism Met allele exacerbates amyloid (Aβ) related decline in episodic memory (EM) and hippocampal volume (HV) over 36-54 months in preclinical Alzheimer's disease (AD). However, the extent to which Aβ+ and BDNF Val66Met is related to circulating markers of BDNF (e.g. serum) is unknown. We aimed to determine the effect of Aβ and the BDNF Val66Met polymorphism on levels of serum mBDNF, EM, and HV at baseline and over 18-months. METHODS: Non-demented older adults (n = 446) underwent Aβ neuroimaging and BDNF Val66Met genotyping. EM and HV were assessed at baseline and 18 months later. Fasted blood samples were obtained from each participant at baseline and at 18-month follow-up. Aβ PET neuroimaging was used to classify participants as Aβ- or Aβ+. RESULTS: At baseline, Aβ+ adults showed worse EM impairment and lower serum mBDNF levels relative to Aβ- adults. BDNF Val66Met polymorphism did not affect serum mBDNF, EM, or HV at baseline. When considered over 18-months, compared to Aβ- Val homozygotes, Aβ+ Val homozygotes showed significant decline in EM and HV but not serum mBDNF. Similarly, compared to Aβ+ Val homozygotes, Aβ+ Met carriers showed significant decline in EM and HV over 18-months but showed no change in serum mBDNF. CONCLUSION: While allelic variation in BDNF Val66Met may influence Aβ+ related neurodegeneration and memory loss over the short term, this is not related to serum mBDNF. Longer follow-up intervals may be required to further determine any relationships between serum mBDNF, EM, and HV in preclinical AD. SN - 1741-203X UR - https://www.unboundmedicine.com/medline/citation/28720165/BDNF_Val66Met_in_preclinical_Alzheimer's_disease_is_associated_with_short_term_changes_in_episodic_memory_and_hippocampal_volume_but_not_serum_mBDNF_ L2 - https://www.cambridge.org/core/product/identifier/S1041610217001284/type/journal_article DB - PRIME DP - Unbound Medicine ER -