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.
Original language | English (US) |
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Pages (from-to) | 205-211 |
Number of pages | 7 |
Journal | Gerontology |
Volume | 64 |
Issue number | 3 |
DOIs | |
State | Published - Mar 1 2018 |
Keywords
- Alzheimer's disease
- Blood-brain barrier
- Cerebral blood flow
- MTOR
- Neurovascular coupling
- Rapamycin
- Vascular density
ASJC Scopus subject areas
- Aging
- Geriatrics and Gerontology