PMID- 22212405
OWN - NLM
STAT- MEDLINE
DCOM- 20130124
LR  - 20120410
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 33
IP  - 6
DP  - 2012 Jun
TI  - The early events of Alzheimer's disease pathology: from mitochondrial dysfunction 
      to BDNF axonal transport deficits.
PG  - 1122.e1-10
LID - 10.1016/j.neurobiolaging.2011.11.004 [doi]
AB  - Although there are numerous studies regarding Alzheimer's disease (AD), the cause 
      and progression of AD are still not well understood. The researches in the past 
      decade implicated amyloid-beta (Abeta) overproduction as a causative event in 
      disease pathogenesis, but still failed to clarify the mechanism of pathology from 
      Abeta production to central neural system defects in AD. The present review raises 
      the hypothesis that the onset of AD pathology is closely related with 
      mitochondrial dysfunction induced by Abeta and brain-derived neurotrophic factor 
      (BDNF) axonal transport deficits. It is well-known that axonal transport defect 
      and attenuation of BDNF-neurotrophic tyrosine receptor kinase 2 (TrkB) signal are 
      fatal to neuronal function and survival. We hypothesized that abnormal amyloid 
      precursor protein (APP) processing and Abeta production in mitochondria disturb the 
      axonal transport by impairing mitochondrial function and attenuate 
      BDNF-neurotrophic tyrosine receptor kinase 2 signal subsequently. For this 
      hypothesis, the factors related with the initiation of AD pathology are not only 
      limited to the neurons per se but also expanded to the microenvironment around 
      neurons, such as the secretion of BDNF from astrocytes. The modification of the 
      origin in this pathway may contribute to slow down the disease progression of AD.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Ye, Xuan
AU  - Ye X
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing, China.
FAU - Tai, Wenjiao
AU  - Tai W
FAU - Zhang, Dan
AU  - Zhang D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20111231
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Alzheimer Disease/genetics/*metabolism/*pathology
MH  - Amyloid beta-Peptides/physiology
MH  - Animals
MH  - Axonal Transport/*genetics
MH  - Brain-Derived Neurotrophic Factor/*deficiency/genetics/physiology
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Humans
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*pathology/physiology
MH  - Neural Inhibition/genetics
EDAT- 2012/01/04 06:00
MHDA- 2013/01/25 06:00
CRDT- 2012/01/04 06:00
PHST- 2011/07/27 00:00 [received]
PHST- 2011/11/01 00:00 [revised]
PHST- 2011/11/04 00:00 [accepted]
PHST- 2012/01/04 06:00 [entrez]
PHST- 2012/01/04 06:00 [pubmed]
PHST- 2013/01/25 06:00 [medline]
AID - S0197-4580(11)00475-1 [pii]
AID - 10.1016/j.neurobiolaging.2011.11.004 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2012 Jun;33(6):1122.e1-10. doi: 
      10.1016/j.neurobiolaging.2011.11.004. Epub 2011 Dec 31.