title: Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer's disease.
abstract: 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.
authors: Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, China.
authors: Yong-Xin
authors: YX
authors: Sun
authors: Xunming
authors: X
authors: Ji
authors: Xiaoou
authors: X
authors: Mao
authors: Lin
authors: L
authors: Xie
authors: Jianping
authors: J
authors: Jia
authors: Veronica
authors: V
authors: Galvan
authors: David A
authors: DA
authors: Greenberg
authors: Kunlin
authors: K
authors: Jin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology*; D000818:Animals; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D011180:Postmortem Changes; D011569:Psychiatric Status Rating Scales; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases
keywords: Alzheimer's disease; RagC; cognitive impairment; mTOR; rapamycin