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

Document Type

Journal Article




Faculty of Health, Engineering and Science


School of Medical Sciences/Centre of Excellence for Alzheimer's Disease Research and Care




This article was originally published as: Lim, Y., Villemagne, V., Laws, S. , Ames, D., Pietrzak, R., Ellis, K., Harrington, K., Bourgeat, P., Salvado, O., Darby, D., Snyder, P., Bush, A., Martins, R. N., Masters, C., Rowe, C., Nathan, P., & Maruff, P. (2013). BDNF Val66Met, Aβ amyloid, and cognitive decline in preclinical Alzheimer's disease. Neurobiology of Aging, 34(11), 2457-2464. Original article available here


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 BDNFVal66Met 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. BDNFVal66Met was not found to be related to rates of change in cognition or hippocampal volume in healthy adults with low Aβ. BDNFVal66Met 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.