PMID- 24086677
OWN - NLM
STAT- MEDLINE
DCOM- 20140718
LR  - 20240313
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 9
DP  - 2013
TI  - Characterizing the role of brain derived neurotrophic factor genetic variation in 
      Alzheimer's disease neurodegeneration.
PG  - e76001
LID - 10.1371/journal.pone.0076001 [doi]
LID - e76001
AB  - There is accumulating evidence that neurotrophins, like brain-derived 
      neurotrophic factor (BDNF), may impact aging and Alzheimer's Disease. However, 
      traditional genetic association studies have not found a clear relationship 
      between BDNF and AD. Our goal was to test whether BDNF single nucleotide 
      polymorphisms (SNPs) impact Alzheimer's Disease-related brain imaging and 
      cognitive markers of disease. We completed an imaging genetics study on 645 
      Alzheimer's Disease Neuroimaging Initiative participants (ND=175, MCI=316, 
      AD=154) who had cognitive, brain imaging, and genetics data at baseline and a 
      subset of those with brain imaging data at two years. Samples were genotyped 
      using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the 
      dataset following quality control measures (rs6265(Val66Met), rs12273363, 
      rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211, 
      rs7934165, rs908867, rs1491850, rs1157459). We analyzed a subgroup of 8 SNPs that 
      were in low linkage disequilibrium with each other. Automated brain morphometric 
      measures were available through ADNI investigators, and we analyzed baseline 
      cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal 
      and whole brain atrophy and rates of change in the ADAS-Cog over one and two 
      years. Three out of eight BDNF SNPs analyzed were significantly associated with 
      measures of cognitive decline (rs1157659, rs11030094, rs11030108). No SNPs were 
      significantly associated with baseline brain volume measures, however six SNPs 
      were significantly associated with hippocampal and/or whole brain atrophy over 
      two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850). We 
      also found an interaction between the BDNF Val66Met SNP and age with whole brain 
      volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF 
      genetic variation is not specifically associated with a diagnosis of AD, it 
      appears to play a role in AD-related brain neurodegeneration.
FAU - Honea, Robyn A
AU  - Honea RA
AD  - Department of Neurology, University of Kansas Alzheimer's Disease Center, 
      University of Kansas Medical Center, Kansas City, Kansas, United States of 
      America.
FAU - Cruchaga, Carlos
AU  - Cruchaga C
FAU - Perea, Rodrigo D
AU  - Perea RD
FAU - Saykin, Andrew J
AU  - Saykin AJ
FAU - Burns, Jeffrey M
AU  - Burns JM
FAU - Weinberger, Daniel R
AU  - Weinberger DR
FAU - Goate, Alison M
AU  - Goate AM
CN  - Alzheimer's Disease Neuroimaging Initiative (ADNI)
LA  - eng
GR  - R01 AG019771/AG/NIA NIH HHS/United States
GR  - R01AG19771/AG/NIA NIH HHS/United States
GR  - U01 AG032984/AG/NIA NIH HHS/United States
GR  - U24AG021886/AG/NIA NIH HHS/United States
GR  - P30AG010133/AG/NIA NIH HHS/United States
GR  - U01AG032984/AG/NIA NIH HHS/United States
GR  - P30 AG010129/AG/NIA NIH HHS/United States
GR  - P30 AG010133/AG/NIA NIH HHS/United States
GR  - U24 AG021886/AG/NIA NIH HHS/United States
GR  - U01 AG024904/AG/NIA NIH HHS/United States
GR  - P30 AG035982/AG/NIA NIH HHS/United States
GR  - CAPMC/CIHR/Canada
GR  - K01 AG035042/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130926
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Age Factors
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*genetics/*physiopathology
MH  - Brain/*physiopathology
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Cognition/*physiology
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Magnetic Resonance Imaging
MH  - Male
MH  - Organ Size/physiology
MH  - Polymorphism, Single Nucleotide/*genetics
PMC - PMC3784423
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/10/03 06:00
MHDA- 2014/07/19 06:00
PMCR- 2013/09/26
CRDT- 2013/10/03 06:00
PHST- 2013/06/27 00:00 [received]
PHST- 2013/08/23 00:00 [accepted]
PHST- 2013/10/03 06:00 [entrez]
PHST- 2013/10/03 06:00 [pubmed]
PHST- 2014/07/19 06:00 [medline]
PHST- 2013/09/26 00:00 [pmc-release]
AID - PONE-D-13-26705 [pii]
AID - 10.1371/journal.pone.0076001 [doi]
PST - epublish
SO  - PLoS One. 2013 Sep 26;8(9):e76001. doi: 10.1371/journal.pone.0076001. eCollection 
      2013.