Effect of BDNF Val66Met on Memory Decline and Hippocampal Atrophy in Prodromal Alzheimer’s Disease: A Preliminary Study
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OBJECTIVE: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. METHODS: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments. RESULTS: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401). CONCLUSIONS: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.
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High Aβ and BDNF Val66Met polymorphism in prodromal AD are linked and suggested as important prognostic markers of increased memory decline and hippocampal atrophy.
“While increased memory decline and hippocampal atrophy have been reported previously in adults with an MCI and high Aβ, Lim et al., (2014) provided a preliminary report and linked high Aβ and BDNF Val66Met polymorphism in prodromal AD suggesting them as important prognostic markers of increased memory decline and hippocampal atrophy [73].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [73]
BDNFMet carriers exhibited greater memory decline and hippocampal atrophy over 36 months compared to BDNF Val homozygotes.
“In another study, BDNFMet carriers exhibited greater memory decline and hippocampal atrophy in a span of 36 months compared to BDNF Val homozygotes.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [73]
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- Authors
- Lim, Y. Y., Villemagne, V. L., Laws, S. M., Ames, D., Pietrzak, R. H., Ellis, K. A., Harrington, K., Bourgeat, P., Bush, A. I., Martins, R. N., Masters, C. L., Rowe, C. C., Maruff, P., & for the AIBL Research Group
- Affiliations
- The University of Melbourne (AU)
- Edith Cowan University (AU)
- Yale University (US)
- Australian e-Health Research Centre (AU)
- Corresponding author
- Lim, Yen Ying
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-01-27
- Volume
- 9
- Issue
- 1
- Pages
- e86498
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3903533
- OpenAlex
- W2035761246
- Cited by
- 110
- References
- 33
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 8 · 2022: 4 · 2021: 11 · 2020: 14 · 2019: 10 · 2018: 9 · 2017: 14 · 2016: 12 · 2015: 14 · 2014: 5
- FWCI
- 11.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- Australasian Journal of Paramedicine (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Minerva Access (University of Melbourne) (submittedVersion)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Science and Industry Endowment Fund
- Australian Government
- Edith Cowan University
- Dementia Collaborative Research Centres, Australia
- Elan
- H. Lundbeck A/S
- Avid Radiopharmaceuticals
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- BDNF Val66Met polymorphism, brain-derived neurotrophic factor, prodromal Alzheimer's disease, amnestic mild cognitive impairment, episodic memory decline, hippocampal atrophy, hippocampal volume, amyloid-beta deposition, genetic risk factors, prognostic factors
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Australia, Cross-Sectional Studies, Female, Genotype, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Amyloid beta-Peptides, Brain-Derived Neurotrophic Factor, Mutation, Missense, Positron-Emission Tomography, Genetic Association Studies, Cognitive Dysfunction
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