BDNF VAL66MET polymorphism and memory decline across the spectrum of Alzheimer's disease
Document Type
Journal Article
Publication Title
Genes, Brain and Behavior
Publisher
Wiley
School
Centre for Precision Health / School of Medical and Health Sciences
RAS ID
32581
Funders
National Health and Medical Resaerch Council Austin Health, CogState Ltd., Sarich Institute Florey Institute, University of Melbourne Edith Cowan University Australian Commonwealth Scientific and Industrial Research Organisation
Grant Number
NHMRC Number : GNT1162645, GNT1147465
Grant Link
http://purl.org/au-research/grants/nhmrc/GNT1162645 http://purl.org/au-research/grants/nhmrc/GNT1147465
Abstract
© 2020 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism has been shown to moderate the extent to which memory decline manifests in preclinical Alzheimer's disease (AD). To date, no study has examined the relationship between BDNF and memory in individuals across biologically confirmed AD clinical stages (i.e., Aβ+). We aimed to understand the effect of BDNF on episodic memory decline and clinical disease progression over 126 months in individuals with preclinical, prodromal and clinical AD. Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were Aβ + (according to positron emission tomography), and cognitively normal (CN; n = 238), classified as having mild cognitive impairment (MCI; n = 80), or AD (n = 66) were included in this study. Cognition was evaluated at 18 month intervals using an established episodic memory composite score over 126 months. We observed that in Aβ + CNs, Met66 was associated with greater memory decline with increasing age and were 1.5 times more likely to progress to MCI/AD over 126 months. In Aβ + MCIs, there was no effect of Met66 on memory decline or on disease progression to AD over 126 months. In Aβ + AD, Val66 homozygotes showed greater memory decline, while Met66 carriers performed at a constant and very impaired level. Our current results illustrate the importance of time and disease severity to clinicopathological models of the role of BDNF Val66Met in memory decline and AD clinical progression. Specifically, the effect of BDNF on memory decline is greatest in preclinical AD and reduces as AD clinical disease severity increases.
DOI
10.1111/gbb.12724
Access Rights
subscription content
Comments
Lim, Y. Y., Laws, S. M., Perin, S., Pietrzak, R. H., Fowler, C., Masters, C. L., & Maruff, P. (2021). BDNF VAL66MET polymorphism and memory decline across the spectrum of Alzheimer's disease. Genes, Brain and Behavior, 20(5), article e12724. https://doi.org/10.1111/gbb.12724