PMID- 23979023
OWN - NLM
STAT- MEDLINE
DCOM- 20140627
LR  - 20211203
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 38
IP  - 2
DP  - 2014
TI  - Differential activation of mTOR complex 1 signaling in human brain with mild to 
      severe Alzheimer's disease.
PG  - 437-44
LID - 10.3233/JAD-131124 [doi]
AB  - Mammalian target of rapamycin (mTOR) signaling has been suggested to be effective 
      in modifying cognitive status in animal models of Alzheimer's disease (AD), but 
      little is known about its role in AD patients. We hereby tested whether mTOR 
      signaling was activated and whether activated mTOR signaling was related to the 
      degree of cognitive deficits in patients with AD. Autopsy brain hippocampal 
      tissues were obtained from controls and patients with AD and Western blots were 
      performed using antibodies against mTOR signaling molecules and RagC, an upstream 
      component of mTOR complex 1 (mTORC1) signaling. We found that expression of 
      mTOR/p-mTOR and its downstream targets S6/p-S6 and Raptor/p-Raptor were expressed 
      in the control and AD hippocampus. The expression levels of these signaling 
      molecules were significantly increased in the hippocampus at the severe stages of 
      AD, compared to controls and other stages of AD. Interestingly, Rictor expression 
      level was unaltered. In addition, RagC was increased in the hippocampus at the 
      early, moderate, and severe stages of AD. Our data indicate that mTORC1, but not 
      mTORC2, was activated in the AD brains and that the level of mTOR signaling 
      activation was correlated with cognitive severity of AD patients.
FAU - Sun, Yong-Xin
AU  - Sun YX
AD  - Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, 
      China.
FAU - Ji, Xunming
AU  - Ji X
FAU - Mao, Xiaoou
AU  - Mao X
FAU - Xie, Lin
AU  - Xie L
FAU - Jia, Jianping
AU  - Jia J
FAU - Galvan, Veronica
AU  - Galvan V
FAU - Greenberg, David A
AU  - Greenberg DA
FAU - Jin, Kunlin
AU  - Jin K
LA  - eng
GR  - I01 BX002211/BX/BLRD VA/United States
GR  - AG21980/AG/NIA NIH HHS/United States
GR  - NS057186/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Alzheimer Disease/complications/*pathology
MH  - Animals
MH  - Cognition Disorders/etiology/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Hippocampus/drug effects/*metabolism
MH  - Humans
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Multiprotein Complexes/*metabolism
MH  - Nerve Tissue Proteins
MH  - Postmortem Changes
MH  - Psychiatric Status Rating Scales
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Young Adult
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - RagC
OT  - cognitive impairment
OT  - mTOR
OT  - rapamycin
EDAT- 2013/08/28 06:00
MHDA- 2014/06/28 06:00
CRDT- 2013/08/28 06:00
PHST- 2013/08/28 06:00 [entrez]
PHST- 2013/08/28 06:00 [pubmed]
PHST- 2014/06/28 06:00 [medline]
AID - 84400H912W7J6558 [pii]
AID - 10.3233/JAD-131124 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2014;38(2):437-44. doi: 10.3233/JAD-131124.