PMID- 24475133
OWN - NLM
STAT- MEDLINE
DCOM- 20141112
LR  - 20240320
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 1
DP  - 2014
TI  - Effect of BDNF Val66Met on memory decline and hippocampal atrophy in prodromal 
      Alzheimer's disease: a preliminary study.
PG  - e86498
LID - 10.1371/journal.pone.0086498 [doi]
LID - e86498
AB  - 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 Abeta accumulation in adults with amnestic mild 
      cognitive impairment (aMCI) and high Abeta. 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 Abeta, 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 Abeta accumulation (d = -0.35, p = .401). CONCLUSIONS: Although preliminary due 
      to the small sample size, results of this study suggest that high Abeta 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.
FAU - Lim, Yen Ying
AU  - Lim YY
AD  - Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Villemagne, Victor L
AU  - Villemagne VL
AD  - 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.
FAU - Laws, Simon M
AU  - Laws SM
AD  - 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.
FAU - Ames, David
AU  - Ames D
AD  - Academic Unit for Psychiatry of Old Age, Department of Psychiatry, The University 
      of Melbourne, Kew, Victoria, Australia ; National Ageing Research Institute, 
      Parkville, Victoria, Australia.
FAU - Pietrzak, Robert H
AU  - Pietrzak RH
AD  - Department of Psychiatry, Yale University School of Medicine, New Haven, 
      Connecticut, United States of America.
FAU - Ellis, Kathryn A
AU  - Ellis KA
AD  - 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.
FAU - Harrington, Karra
AU  - Harrington K
AD  - Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Bourgeat, Pierrick
AU  - Bourgeat P
AD  - Commonwealth Scientific Industrial Research Organization Preventative Health 
      National Research Flagship, Australian e-Health Research Centre-BioMedIA, 
      Brisbane, Queensland, Australia.
FAU - Bush, Ashley I
AU  - Bush AI
AD  - Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Martins, Ralph N
AU  - Martins RN
AD  - 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.
FAU - Masters, Colin L
AU  - Masters CL
AD  - Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 
      Parkville, Victoria, Australia.
FAU - Rowe, Christopher C
AU  - Rowe CC
AD  - 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.
FAU - Maruff, Paul
AU  - Maruff P
AD  - Florey Institute of Neuroscience and Mental Health, The University of Melbourne, 
      Parkville, Victoria, Australia ; CogState Ltd., Melbourne, Victoria, Australia.
CN  - AIBL Research Group
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140127
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*genetics
MH  - Amyloid beta-Peptides/metabolism
MH  - Atrophy
MH  - Australia
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cognitive Dysfunction/genetics/*pathology
MH  - Cross-Sectional Studies
MH  - Female
MH  - Genetic Association Studies
MH  - Genotype
MH  - Hippocampus/*pathology
MH  - Humans
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Memory Disorders/*genetics
MH  - Mutation, Missense/genetics
MH  - Positron-Emission Tomography
PMC - PMC3903533
COIS- Competing Interests: YYL, SML, KE, RP, KH, PB, OS, CM and PM report no 
      disclosures. VV serves as a consultant for Bayer Schering Pharma; and receives 
      research support from NEDO, Japan. DA has served on scientific advisory boards 
      for Novartis, Eli Lilly, Janssen, and Pfizer Inc.; has received funding for 
      travel from Janssen and Pfizer Inc.; has received speaker honoraria from Pfizer 
      Inc. and Lundbeck Inc.; and has received research support from Eli Lilly and 
      Company, GlaxoSmithKline, Forest Laboratories Inc., and Novartis. AB is a paid 
      consultant for Synthetic Biologics, and holds equity in Prana Biotechnology Ltd, 
      CogState Ltd., and Eucalyptus Biosciences Pty Ltd. RM is a consultant to Alzhyme. 
      CR serves on scientific advisory boards for Bayer Schering Pharma, Elan 
      Corporation, and AstraZeneca; has received speaker honoraria from Bayer Schering 
      Pharma; and receives research support from Bayer Schering Pharma, and Avid 
      Radiopharmaceuticals, Inc. PM is a full-time employee of CogState Ltd. Simon Laws 
      is supported by the Cooperative Research Centre for Mental Health, which is an 
      Australian Response to Reviewers government initiative. This does not alter the 
      authors' adherence to all the PLOS ONE policies on sharing data and materials.
EDAT- 2014/01/30 06:00
MHDA- 2014/11/13 06:00
PMCR- 2014/01/27
CRDT- 2014/01/30 06:00
PHST- 2013/07/08 00:00 [received]
PHST- 2013/12/10 00:00 [accepted]
PHST- 2014/01/30 06:00 [entrez]
PHST- 2014/01/30 06:00 [pubmed]
PHST- 2014/11/13 06:00 [medline]
PHST- 2014/01/27 00:00 [pmc-release]
AID - PONE-D-13-28201 [pii]
AID - 10.1371/journal.pone.0086498 [doi]
PST - epublish
SO  - PLoS One. 2014 Jan 27;9(1):e86498. doi: 10.1371/journal.pone.0086498. eCollection 
      2014.