PMID- 22342520
OWN - NLM
STAT- MEDLINE
DCOM- 20120816
LR  - 20131121
IS  - 1873-4596 (Electronic)
IS  - 0891-5849 (Linking)
VI  - 52
IP  - 8
DP  - 2012 Apr 15
TI  - Early memory deficits precede plaque deposition in APPswe/PS1dE9 mice: 
      involvement of oxidative stress and cholinergic dysfunction.
PG  - 1443-52
LID - 10.1016/j.freeradbiomed.2012.01.023 [doi]
AB  - A large body of evidence has shown that cognitive deficits occur early, before 
      amyloid plaque deposition, suggesting that soluble amyloid-beta protein (Abeta) 
      contributes to the development of early cognitive dysfunction in Alzheimer 
      disease (AD). However, the underlying mechanism(s) through which soluble Abeta 
      exerts its neurotoxicity responsible for cognitive dysfunction in the early stage 
      of AD remains unclear so far. In this study, we used preplaque APPswe/PS1dE9 mice 
      ages 2.5 and 3.5 months to examine alterations in cognitive function, oxidative 
      stress, and cholinergic function. We found that only soluble Abeta, not insoluble 
      Abeta, was detected in these preplaque APPswe/PS1dE9 mice. APPswe/PS1dE9 mice 2.5 
      months of age did not show any significant changes in the measures of cognitive 
      function, oxidative stress, and cholinergic function, whereas 3.5-month-old 
      APPswe/PS1dE9 mice exhibited spatial memory impairment in the Morris water maze, 
      accompanied by significantly decreased acetylcholine (ACh), choline 
      acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase 
      (GSH-px) as well as increased malondialdehyde (MDA) and protein carbonyls. In 
      3.5-month-old preplaque APPswe/PS1dE9 mice, correlational analyses revealed that 
      the performance of impaired spatial memory was inversely correlated with soluble 
      Abeta, MDA, and protein carbonyls, as well as being positively correlated with ACh, 
      ChAT, SOD, and GSH-px; soluble Abeta level was inversely correlated with ACh, ChAT, 
      SOD, and GSH-px, as well as being positively correlated with MDA and protein 
      carbonyls; ACh level showed a significant positive correlation with ChAT, SOD, 
      and GSH-px, as well as a significant inverse correlation with MDA and protein 
      carbonyls. Collectively, this study provides direct evidence that increased 
      oxidative damage and cholinergic dysfunction may be early pathological responses 
      to soluble Abeta and involved in early memory deficits in the preplaque stage of AD. 
      These findings suggest that early antioxidant therapy and improving cholinergic 
      function may be a promising strategy to prevent or delay the onset and 
      progression of AD.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Neurology, Tangdu Hospital, Fourth Military Medical University, 
      Xi'an City, Shaanxi Province 710038, China.
FAU - Bai, Miao
AU  - Bai M
FAU - Xi, Ye
AU  - Xi Y
FAU - Hao, Jian
AU  - Hao J
FAU - Liu, Liu
AU  - Liu L
FAU - Mao, Ni
AU  - Mao N
FAU - Su, Changjun
AU  - Su C
FAU - Miao, Jianting
AU  - Miao J
FAU - Li, Zhuyi
AU  - Li Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120202
PL  - United States
TA  - Free Radic Biol Med
JT  - Free radical biology & medicine
JID - 8709159
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Receptors, Cholinergic)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Choline O-Acetyltransferase/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glutathione Peroxidase/metabolism
MH  - Malondialdehyde/metabolism
MH  - Maze Learning
MH  - Memory Disorders/metabolism/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - *Oxidative Stress
MH  - Receptors, Cholinergic/*physiology
MH  - Superoxide Dismutase/metabolism
EDAT- 2012/02/22 06:00
MHDA- 2012/08/17 06:00
CRDT- 2012/02/21 06:00
PHST- 2011/06/19 00:00 [received]
PHST- 2012/01/08 00:00 [revised]
PHST- 2012/01/26 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/08/17 06:00 [medline]
AID - S0891-5849(12)00067-6 [pii]
AID - 10.1016/j.freeradbiomed.2012.01.023 [doi]
PST - ppublish
SO  - Free Radic Biol Med. 2012 Apr 15;52(8):1443-52. doi: 
      10.1016/j.freeradbiomed.2012.01.023. Epub 2012 Feb 2.