BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease

Lim, Yen Ying; Villemagne, Victor L.; Laws, Simon M.; Ames, David; Pietrzak, Robert H.; Ellis, Kathryn A.; Harrington, Karra D.; Bourgeat, Pierrick; Salvado, Olivier; Darby, David; Snyder, Peter J.; Bush, Ashley I.; Martins, Ralph N.; Masters, Colin L.; Rowe, Christopher C.; Nathan, Pradeep J.; Maruff, Paul

doi:10.1016/j.neurobiolaging.2013.05.006

Cited by 124Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease

Lim, Yen Ying, Villemagne, Victor L., Laws, Simon M., Ames, David, Pietrzak, Robert H., Ellis, Kathryn A., Harrington, Karra D., Bourgeat, Pierrick +9 more·2013·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2013.05.006

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Abstract

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has previously been implicated in Alzheimer's disease (AD)-related cognitive impairment. We aimed to determine the relationship between BDNF Val66Met and beta-amyloid (Aβ) on cognitive decline, hippocampal atrophy, and Aβ accumulation over 36 months in 165 healthy adults enrolled in the Australian Imaging, Biomarkers and Lifestyle study. In healthy adults with high Aβ, Met carriers showed significant and moderate-to-large declines in episodic memory, executive function, and language, and greater hippocampal atrophy over 36 months, compared with Val/Val homozygotes. BDNF Val66Met was not found to be related to rates of change in cognition or hippocampal volume in healthy adults with low Aβ. BDNF Val66Met did not relate to the amount of Aβ or to the rate of Aβ accumulation in either group. High Aβ levels coupled with Met carriage may be useful prognostic markers of accelerated cognitive decline and hippocampal degeneration in individuals in the preclinical stage of AD.

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In healthy adults with high Aβ and carrying the Met allele, the rate of hippocampal volume reduction was significantly greater.
“In the study conducted in healthy adults having a high Aβ level and carrying the Met allele, the rate of HV reduction was significantly more.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [72]
In Val/Val homozygotes with high Aβ levels, hippocampal volume reduction rate was greater than with low Aβ, irrespective of BDNF Val66Met polymorphism over 36 months.
“A greater reduction rate in HV was observed in Val/Val homozygotes who were having high Aβ levels than with low Aβ, irrespective of their BDNF Val66Met polymorphism over 36 months.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [72]
In healthy individuals, memory decline with reduction in hippocampal volume corresponds with high Aβ levels.
“The decline in memory with the reduction in hippocampal volume (HV) corresponding with high Aβ levels has been already reported in healthy individuals; Lim et al. (2013) showed that BDNF Val66Met worsens these conditions more in the preclinical stage of AD [72].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [72]
BDNF Val66Met worsens memory decline and hippocampal volume reduction in the preclinical stage of AD.
“The decline in memory with the reduction in hippocampal volume (HV) corresponding with high Aβ levels has been already reported in healthy individuals; Lim et al. (2013) showed that BDNF Val66Met worsens these conditions more in the preclinical stage of AD [72].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [72]

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Effect of BDNF Val66Met on Memory Decline and Hippocampal Atrophy in Prodromal Alzheimer’s Disease: A Preliminary Study
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., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086498 · Cited by 110 · see citing works
Self-citation
BDNF VAL66MET polymorphism and memory decline across the spectrum of Alzheimer's disease
Lim, Y. Y., Laws, S. M., Perin, S., Pietrzak, R. H., Fowler, C. J., Masters, C. L., & Maruff, P. T. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12724 · Cited by 24 · see citing works
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BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer's Prevention
Boots, E. A., Schultz, S. A., Clark, L. R., Racine, A. M., Darst, B. F., Koscik, R. L., Carlsson, C. M., Gallagher, C. L., Hogan, K. J., Bendlin, B. B., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000003980 · Cited by 70 · see citing works
BDNF Val66Met in preclinical Alzheimer's disease is associated with short-term changes in episodic memory and hippocampal volume but not serum mBDNF
Lim, Y. Y., Rainey‐Smith, S. R., Lim, Y. P., Laws, S. M., Gupta, V. B., Porter, T., Bourgeat, P., Ames, D. J., Fowler, C. J., Salvado, O., et al. (2017) · International Psychogeriatrics · doi:10.1017/s1041610217001284 · Cited by 25 · see citing works
Self-citation

Authors: Lim, Y. Y., Villemagne, V. L., Laws, S. M., Ames, D., Pietrzak, R. H., Ellis, K. A., Harrington, K. D., Bourgeat, P., Salvado, O., Darby, D., Snyder, P. J., Bush, A. I., Martins, R. N., Masters, C. L., Rowe, C. C., Nathan, P. J., & Maruff, P.
Affiliations: Mental Health Research Institute (AU)
Edith Cowan University (AU)
The University of Melbourne (AU)
Yale University (US)
Australian e-Health Research Centre (AU)
Brown University (US)
GlaxoSmithKline (United Kingdom) (GB)
Corresponding author: Lim, Yen Ying
ORCID: Lim, Yen Ying
Villemagne, Victor L.
Laws, Simon M.
Pietrzak, Robert H.
Ellis, Kathryn A.
Harrington, Karra D.
Bourgeat, Pierrick
Salvado, Olivier
Darby, David
Snyder, Peter J.
Bush, Ashley I.
Martins, Ralph N.
Masters, Colin L.
Nathan, Pradeep J.
Maruff, Paul
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2013-11
Volume: 34
Issue: 11
Pages: 2457-2464
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2013.05.006
OpenAlex: W1998751550
Cited by: 124
References: 40
Citations by year: 2026: 2 · 2025: 6 · 2024: 3 · 2023: 7 · 2022: 7 · 2021: 10 · 2020: 16 · 2019: 12 · 2018: 17 · 2017: 12 · 2016: 11 · 2015: 6 · 2014: 13 · 2013: 2
FWCI: 7.58
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Neurobiology of Aging (publishedVersion)
PubMed (publishedVersion)
Research Online (Edith Cowan University) (submittedVersion)
Swinburne figshare (Swinburne University of Technology) (submittedVersion)
Funders: Australian Commonwealth Scientific Industrial and research Organization
Edith Cowan University
Mental Health Research institute (MHRI), Alzheimer's Australia
National Ageing Research Institute
Austin Health, CogState Ltd.
Hollywood Private Hospital
Sir Charles Gardner Hospital
National Health and Medical Research Council
Dementia Collaborative Research Centres
Science and Industry Endowment Fund
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 › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords: BDNF Val66Met polymorphism, brain-derived neurotrophic factor, amyloid-beta, preclinical Alzheimer's disease, cognitive decline, hippocampal atrophy, episodic memory, executive function, language, amyloid accumulation, prognostic factors
MeSH terms: Aged, Alzheimer Disease, Aniline Compounds, Australia, Cognition Disorders, Female, Genotype, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Methionine, Neuropsychological Tests, Psychiatric Status Rating Scales, Thiazoles, Valine, Amyloid beta-Peptides, Brain-Derived Neurotrophic Factor, Positron-Emission Tomography, Apolipoprotein E4, Memory, Episodic

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BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease

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