Alzheimer's disease (AD) is characterized by
cognitive impairment in clinical presentation, and by β-
amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the
mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by modulating
amyloid precursor
protein (APP) metabolism and upregulating β- and γ-
secretases. mTOR, an inhibitor of autophagy, decreases Aβ clearance by scissoring autophagy function. mTOR regulates Aβ generation or Aβ clearance by regulating several key signaling pathways, including
phosphoinositide 3-kinase (PI3-K)/
protein kinase B (Akt),
glycogen synthase kinase 3 [GSK-3],
AMP-activated protein kinase (AMPK), and
insulin/
insulin-like growth factor 1 (IGF-1). The activation of mTOR is also a contributor to aberrant hyperphosphorylated tau.
Rapamycin, the inhibitor of mTOR, may mitigate
cognitive impairment and inhibit the pathologies associated with
amyloid plaques and neurofibrillary tangles by promoting autophagy. Furthermore, the upstream and downstream components of mTOR signaling are involved in the pathogenesis and progression of AD. Hence, inhibiting the activation of mTOR may be an important therapeutic target for AD.