PMID- 22870188
OWN - NLM
STAT- MEDLINE
DCOM- 20130219
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 8
DP  - 2012
TI  - Genetic knockdown of brain-derived neurotrophic factor in 3xTg-AD mice does not 
      alter Abeta or tau pathology.
PG  - e39566
LID - 10.1371/journal.pone.0039566 [doi]
LID - e39566
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin critically involved in 
      cell survival, synaptic plasticity, and memory. BDNF has recently garnered 
      significant attention as a potential therapeutic target for neurodegenerative 
      diseases such as Alzheimer disease (AD), but emerging evidence suggests that BDNF 
      may also be mechanistically involved in the pathogenesis of AD. AD patients have 
      substantially reduced BDNF levels, which may be a result of Abeta and tau pathology. 
      Recent evidence, however, indicates reduced BDNF levels may also serve to drive 
      pathology in neuronal cultures, although this has not yet been established in 
      vivo. To further investigate the mechanistic role of BDNF in AD, we generated 
      3xTg-AD mice with a heterozygous BDNF knockout (BDNF(+/-)) and analyzed Abeta and 
      tau pathology. Aged 3xTg-AD/BDNF(+/-) mice have significantly reduced levels of 
      brain BDNF, but have comparable levels of Abeta and tau pathology to 
      3xTg-AD/BDNF(+/+) mice. These findings indicate that chronic reduction of BDNF 
      does not exacerbate the development of Abeta and tau pathology, and instead suggests 
      the reduced BDNF levels found in AD patients are a consequence of these 
      pathologies.
FAU - Castello, Nicholas A
AU  - Castello NA
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California Irvine, Irvine, California, United States of America.
FAU - Green, Kim N
AU  - Green KN
FAU - LaFerla, Frank M
AU  - LaFerla FM
LA  - eng
GR  - F31 AG034061/AG/NIA NIH HHS/United States
GR  - P50 AG016573/AG/NIA NIH HHS/United States
GR  - P50 AG16573/AG/NIA NIH HHS/United States
GR  - F31AG034061/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 - 20120803
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (tau Proteins)
SB  - IM
MH  - Alzheimer Disease/genetics/*metabolism/pathology
MH  - Amyloid beta-Peptides/genetics/*metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Humans
MH  - Mice
MH  - Mice, Knockout
MH  - Neurons/*metabolism/pathology
MH  - tau Proteins/genetics/*metabolism
PMC - PMC3411687
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/08/08 06:00
MHDA- 2013/02/21 06:00
PMCR- 2012/08/03
CRDT- 2012/08/08 06:00
PHST- 2012/01/27 00:00 [received]
PHST- 2012/05/27 00:00 [accepted]
PHST- 2012/08/08 06:00 [entrez]
PHST- 2012/08/08 06:00 [pubmed]
PHST- 2013/02/21 06:00 [medline]
PHST- 2012/08/03 00:00 [pmc-release]
AID - PONE-D-12-02863 [pii]
AID - 10.1371/journal.pone.0039566 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(8):e39566. doi: 10.1371/journal.pone.0039566. Epub 2012 Aug 3.