Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal Alzheimer's disease: a preliminary study.
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.
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
Yen Ying
YY
Lim
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia ; Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia ; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
Victor L
VL
Villemagne
Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia ; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia ; Co-operative Research Centre for Mental Health, Carlton South, Australia.
Simon M
SM
Laws
Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia ; National Ageing Research Institute, Parkville, Victoria, Australia.
David
D
Ames
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Robert H
RH
Pietrzak
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia ; Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University of Melbourne, Kew, Victoria, Australia ; National Ageing Research Institute, Parkville, Victoria, Australia.
Kathryn A
KA
Ellis
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
Karra
K
Harrington
Commonwealth Scientific Industrial Research Organization Preventative Health National Research Flagship, Australian e-Health Research Centre-BioMedIA, Brisbane, Queensland, Australia.
Pierrick
P
Bourgeat
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
Ashley I
AI
Bush
Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia ; Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Perth, Western Australia, Australia.
Ralph N
RN
Martins
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia.
Colin L
CL
Masters
Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, Victoria, Australia ; Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
Christopher C
CC
Rowe
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia ; CogState Ltd., Melbourne, Victoria, Australia.
Paul
P
Maruff
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001284:Atrophy; D001315:Australia; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D060825:Cognitive Dysfunction / Q000235:genetics / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D049268:Positron-Emission Tomography
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human