A Perfect sTORm: The Role of the Mammalian Target of Rapamycin (mTOR) in Cerebrovascular Dysfunction of Alzheimer's Disease: A Mini-Review

Gerontology. 2018;64(3):205-211. doi: 10.1159/000485381. Epub 2018 Jan 11.

Abstract

Cerebrovascular dysfunction is detected prior to the onset of cognitive and histopathological changes in Alzheimer's disease (AD). Increasing evidence indicates a critical role of cerebrovascular dysfunction in the initiation and progression of AD. Recent studies identified the mechanistic/mammalian target of rapamycin (mTOR) as a critical effector of cerebrovascular dysfunction in AD. mTOR has a key role in the regulation of metabolism, but some mTOR-dependent mechanisms are uniquely specific to the regulation of cerebrovascular function. These include the regulation of cerebral blood flow, blood-brain barrier integrity and maintenance, neurovascular coupling, and cerebrovascular reactivity. This article examines the available evidence for a role of mTOR-driven cerebrovascular dysfunction in the pathogenesis of AD and of vascular cognitive impairment and dementia (VCID) and highlights the therapeutic potential of targeting mTOR and/or specific downstream effectors for vasculoprotection in AD, VCID, and other age-associated neurological diseases with cerebrovascular etiology.

Keywords: Alzheimer’s disease; Blood-brain barrier; Cerebral blood flow; Neurovascular coupling; Rapamycin; Vascular density; mTOR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / physiopathology*
  • Blood-Brain Barrier / physiopathology
  • Cerebrovascular Circulation / physiology
  • Cerebrovascular Disorders / complications
  • Cerebrovascular Disorders / physiopathology*
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / physiopathology
  • Dementia / etiology
  • Dementia / physiopathology
  • Dementia, Vascular / etiology
  • Humans
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • MTOR protein, human
  • TOR Serine-Threonine Kinases