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

作者：Van Skike Candice E; Galvan Veronica^*

来源：Gerontology, 2018, 64(3): 205-211.

DOI：10.1159/000485381

• Alzheimer's disease
• Blood-brain barrier
• Cerebral blood flow
• mTOR
• Neurovascular coupling
• Rapamycin
• Vascular density

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.

• 出版日期2018