PMID- 22710966
OWN - NLM
STAT- MEDLINE
DCOM- 20120904
LR  - 20211021
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Print)
IS  - 0022-3069 (Linking)
VI  - 71
IP  - 7
DP  - 2012 Jul
TI  - Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in 
      early Alzheimer disease pathology.
PG  - 654-64
LID - 10.1097/NEN.0b013e31825d06b7 [doi]
AB  - Brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B 
      (TrkB) may influence brain reserve, the ability of the brain to tolerate 
      pathological changes without significant decline in function. Here, we explore 
      whether a specifically vulnerable population of human neurons shows a 
      compensatory response to the neuropathological changes of Alzheimer disease (AD) 
      and whether that response depends on an upregulation of the BDNF pathway. We 
      observed increased neuronal TrkB expression associated with early-stage AD 
      pathology (Braak and Braak stages I-II) in hippocampal CA1 region samples from 
      cognitively intact Framingham Heart Study subjects (n = 5) when compared with 
      cognitively intact individuals with no neurofibrillary tangles (n = 4). Because 
      BDNF/TrkB signaling affects memory formation and retention through modification 
      of the actin cytoskeleton, we examined the expression of actin capping protein beta2 
      (Capzb2), a marker of actin cytoskeleton reorganization. Capzb2 expression was 
      also significantly increased in CA1 hippocampal neurons of cognitively intact 
      subjects with early-stage AD pathology. Our data suggest that increased 
      expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial 
      stages of AD pathology. In subsequent stages of AD, the higher levels of TrkB and 
      Capzb2 expression achieved may not be sufficient to prevent cognitive decline.
FAU - Kao, Patricia F
AU  - Kao PF
AD  - Department of Pathology and Laboratory Medicine, Boston University School of 
      Medicine, Boston, MA 02118, USA.
FAU - Banigan, Meredith G
AU  - Banigan MG
FAU - Vanderburg, Charles R
AU  - Vanderburg CR
FAU - McKee, Ann C
AU  - McKee AC
FAU - Polgar, Peter R
AU  - Polgar PR
FAU - Seshadri, Sudha
AU  - Seshadri S
FAU - Delalle, Ivana
AU  - Delalle I
LA  - eng
GR  - R01 NS017950/NS/NINDS NIH HHS/United States
GR  - P30 AG013846/AG/NIA NIH HHS/United States
GR  - R01AG08122/AG/NIA NIH HHS/United States
GR  - R01 AG008122/AG/NIA NIH HHS/United States
GR  - R01 AG033193/AG/NIA NIH HHS/United States
GR  - P30AG013846/AG/NIA NIH HHS/United States
GR  - 5T32AG000115-25/AG/NIA NIH HHS/United States
GR  - T32 AG000115/AG/NIA NIH HHS/United States
GR  - R01AG033193/AG/NIA NIH HHS/United States
GR  - R01AG031287/AG/NIA NIH HHS/United States
GR  - R01 AG031287/AG/NIA NIH HHS/United States
GR  - R01AG16495/AG/NIA NIH HHS/United States
GR  - R01 AG016495/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (Actin Capping Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Actin Capping Proteins/genetics/*metabolism
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/*complications/*pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Cognition Disorders/diagnosis/*etiology
MH  - Dementia/complications
MH  - Female
MH  - Hippocampus/*metabolism
MH  - Humans
MH  - Laser Capture Microdissection
MH  - Male
MH  - Neuropsychological Tests
MH  - RNA, Messenger/metabolism
MH  - Receptor, trkB/genetics/*metabolism
MH  - Signal Transduction/physiology
MH  - Silver Staining
MH  - Up-Regulation/physiology
PMC - PMC3398703
MID - NIHMS385455
EDAT- 2012/06/20 06:00
MHDA- 2012/09/05 06:00
PMCR- 2013/07/01
CRDT- 2012/06/20 06:00
PHST- 2012/06/20 06:00 [entrez]
PHST- 2012/06/20 06:00 [pubmed]
PHST- 2012/09/05 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - 10.1097/NEN.0b013e31825d06b7 [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2012 Jul;71(7):654-64. doi: 
      10.1097/NEN.0b013e31825d06b7.