Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease

BACKGROUND: Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1], [2], [3], [4]. It was recently demonstrated that long-term treatment with rapamycin, an inhibitor of the mTOR pathway[5], or ablation of the mTOR target p70S6K[6] extends lifespan in mice, possibly by delaying aging. Whether inhibition of the mTOR pathway would delay or prevent age-associated disease such as AD remained to be determined. METHODOLOGY/PRINCIPAL FINDINGS: We used rapamycin administration and behavioral tools in a mouse model of AD as well as standard biochemical and immunohistochemical measures in brain tissue to provide answers for this question. Here we show that long-term…

• UD
  U.S. Department of Veterans Affairs
• AA
  Alzheimer's Association

  Award: NIRG-DDC-120433
• BI
  Buck Institute for Research on Aging
• UO
  University of Texas Health Science Center at San Antonio
• NI
  National Institute on Aging

  Award: U01AG022307