Affiliations: [a] Department of Neurology, Xuan Wu Hospital of Capital Medical University, Beijing, China | [b] Department of Neurosurgery, Xuan Wu Hospital of Capital Medical University, Beijing, China | [c] Buck Institute for Research on Aging, Novato, CA, USA | [d] Department of Physiology and the Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, TX, USA | [e] Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA
Correspondence:
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Correspondence to: Kunlin Jin, Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA. Tel.: +1 817 735 2579; E-mail: Kunlin.Jin@unthsc.edu.
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.
